Body Shakes Research Articles

Produção de formas aladas em colônias de Brevicoryne brassicae (L.) (Hemiptera: Aphididae) por indução do parasitóide Diaeretiella rapae (McIntosh) (Hymenoptera: Aphidiidae) e alguns aspectos comportamentais da interação destas espécies

O objetivo deste trabalho foi o de verificar se há indução de indivíduos alados em colônias de Brevicoryne brassicae (L.), quando expostas a Diaeretiella rapae (McIntosh). Foram também descritos alguns aspectos das interações biológicas dessas espécies. Colônias do pulgão foram iniciadas com 10 adultos por planta de couve, isoladas em recipientes transparentes. Um casal de parasitóides foi introduzido e mantido dentro de cada recipiente-teste por 3h; não foram introduzidos parasitóides do grupo controle. Formas aladas foram produzidas tanto na presença como na ausência de parasitóides, mas, na sua presença, os pulgões alados foram produzidos mais rapidamente e em número significativamente maior. Não se obteve correlação significativa entre o número de alados e o número de múmias. A longevidade média foi de 2,3 ± 0,19 dias e a taxa de parasitoidismo foi em média de 20,6 ± 5,21%. B. brassicae respondeu à presença de D. rapae com aumento na produção de formas aladas. Isto pode ser considerado um mecanismo de defesa, pois os pulgões poderiam, estrategicamente, manter sua sobrevivência, escapando pelo vôo e colonizando outras plantas hospedeiras. Dois outros comportamentos de defesas foram registrados: agitação vigorosa do corpo e fuga dos parasitóides. Durante 26h de observação, foram catalogados 20 atos comportamentais de D. rapae, divididos em cinco categorias: auto-limpeza, alimentação, exploração, cópula e oviposição. Interações diretas entre as espécies ocorreram não somente durante a oviposição, mas também quando a vespa tocava os pulgões com as antenas e ovipositor.

Neurotoxicity of Diethylpropion

The effects of diethylpropion (DEP), an amphetamine derivative and a well-known anorectic agent, on different neurochemical and behavioral markers of toxicity in rats were evaluated. Animals received a daily dose of DEP (5 mg/kg po) for 15 days, and all tests were performed 24 hours after the last DEP administration. As neurochemical markers, the brain regional levels of some amino acids, such as aspartate (Asp), glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln), as well as the brain regional rates of lipid peroxidation as a current index of oxidative stress were measured. As behavioral markers, the actions of DEP on both mercaptopropionic acid (MPA)-induced seizures and kainic acid (KA)-induced wet-dog body shakes were explored to investigate whether DEP induces behavioral sensitization to the effects of agents affecting the central activity of neuroactive amino acids. Treatment with DEP produced significant changes in the levels of Asp in the hypothalamus (Ht) and cortex (Cx); Glu in the Ht, Cx, midbrain (Mb), and striatum (S); and Gln in the Cx. The regional levels of GABA remain unchanged. Lipid peroxidation was increased in the hippocampus (Hc), Mb, and S. Also, latency to the first seizure induced by MPA (1.2 mmol/kg i.p.) and the total number of wet-dog body shakes induced by KA (10 mg/kg i.p.) were significantly affected by DEP treatment. These findings suggest that low doses of DEP may affect different neurochemical substrates, inducing changes in neuroactive amino acids along the brain regions, probably involving dopamine release. Consequently, behavioral changes could be the result of excitotoxic events related to excessive Glu or lack of an inhibitory process. Also, DEP is thought to involve free radical formation and oxidative stress as potential features of its regional pattern of neurotoxicity, as evidenced by lipid peroxidation.

A novel behavioral model that discriminates between 5-HT 2A and 5-HT 2C receptor activation

2,5-Dimethoxy-4-iodoamphetamine (DOI), a serotonin (5-HT) 2A/2C receptor agonist, elicits shaking behaviors in rodents, which have been reliably quantified as behavioral correlates of 5-HT 2A receptor activation. Such studies are lacking in the rabbit. As part of our research examining the role of the 5-HT 2 receptor in rabbits, we analyzed the behavioral effects of systemically administered DOI in rabbits. DOI (0.01–3 μmol/kg) or vehicle was injected, and two distinct behaviors, head bobs (vertical head movements) and body shakes (wet dog shakes), were counted for 90 min following the injection. DOI dose-dependently increased the number of head bobs and body shakes. The selective 5-HT 2A receptor antagonist ketanserin (1–3 μmol/kg), 1 h before DOI (0.3 μmol/kg) challenge, significantly attenuated head bobs, but not body shakes. In contrast, the selective 5-HT 2C receptor antagonists SDZ SER 082 (1–3 μmol/kg) and SB 206553 (1 μmol/kg) 30 min before challenge, significantly reduced body shakes but not head bobs produced by the same dose of DOI. This study establishes that, in rabbits, DOI mediates head bobs via 5-HT 2A receptors and body shakes via 5-HT 2C receptors. Thus, the rabbit provides a novel behavioral assay that discriminates between 5-HT 2A and 5-HT 2C receptor activation.

Ethological analysis of morphine withdrawal with different dependence programs in male mice

This work was performed to clarify the differences between a long or short development of morphine dependence as well as between a recently installed or a long-term dependence. Morphine withdrawal in rats is a well-characterized phenomenon but this is not so in mice. A study of the principal withdrawal signs have been performed in mice, evaluating their specificity and particular profile of appearance in each type of dependence. Mice were divided into two groups that received increasing doses of morphine every 24 h, three groups that received increasing doses of morphine twice a day for 3 days, and a control group that received saline. Naloxone-induced opiate withdrawal was evaluated following short-term exposition to morphine [Test 1 (T1)—saline and Test 2 (T2)—naloxone] and long-term exposition to morphine [Test 3 (T3)—naloxone and Test 4 (T4)—saline]. Morphine administration twice a day is more effective in inducing opiate dependence than once a day, and with the latter, the duration of morphine exposure increases the intensity of withdrawal signs. Weight loss, diarrhea, body shakes, jumping, paw tremor, ptosis, piloerection, and the modified Gellert–Holtzman scale for mice are specific patterns of naloxone-induced withdrawal. The first four signs allow the discrimination between different levels of opiate dependence. Body care, piloerection, and the modified Gellert–Holtzman scale could be useful to detect conditioned withdrawal.

Behavioural and Hormonal Indicators of Enduring Environmental Stress in Dogs

AbstractFour groups of dogs, which had been subjected to housing conditions of varying quality for years, were assumed to experience different levels of stress. The groups were compared for behavioural and hormonal parameters in order to identify measures that indicate chronic stress in the dog and which may help to identify poor welfare in this species. As a standard for comparison, one of the four groups was composed of privately owned dogs; we assumed that chronic stress levels were relatively low in this group (GI). The three remaining groups of dogs (GII, Gill and GIV) were kept under conditions of low to relatively high austerity, and had basal urinary ratios of Cortisol to creatinine, adrenaline to creatinine and, to a lesser extent, noradrenaline to creatinine, that varied from low to high, respectively. Significant differences (P < 0.05) were found in Cortisol to creatinine ratios when comparing GI to GII, GUI and GIV and when GII was compared to GIV. Statistical analyses indicated that the mean adrenaline to creatinine ratio in GI differed from that in the remaining groups and that the ratio in GII differed from that in GUI. Noradrenaline to creatinine ratios differed significantly only between GI and GUI. Dopamine to creatinine ratios and noradrenaline to adrenaline ratios did not differ significantly between groups. When dogs were not disturbed, those that were kept under the most austere conditions typically had high levels of locomotor activity, nosing, urinating and paw lifting. After mild disturbance by a slamming door or in the presence of a researcher these animals reacted actively, with increased locomotor activity, circling and nosing, and they showed high levels of behaviours that have previously been associated with acute stress: body shaking, yawning, ambivalent postures and displacement behaviours. Chronic stress in dogs may be identified by increased paw lifting when animals are not disturbed and by ample behavioural expressions of arousal when they are mildly stimulated. Since some behaviours may occur in contexts not related to stress, behavioural data are easily misinterpreted with regard to chronic stress. Interpretation will only be meaningful when physiological measures such as urinary adrenaline to creatinine ratios and, especially, urinary Cortisol to creatinine ratios are also determined.

Social anxiety, relationships and self-directed behaviour among wild female olive baboons

Self-directed behaviour (SDB) can be used as a behavioural indicator of stress and anxiety in nonhuman primates (Maestripieri et al. 1992, Animal Behaviour, 44, 967–979). We investigated the effect of nearest neighbours' relative dominance status on the SDB of sexually mature female olive baboons, Papio anubis. When the animal nearest to (within 5m of) a female was a dominant individual, SDB rates (a combined measure of self-scratching, self-grooming, self-touching, body shaking and yawning) increased by ca.40% over those observed when the nearest neighbour was a subordinate. The results indicate that (1) SDB can be used as a measure of uncertainty during the social interactions of cercopithecine primates and (2) as there was considerable variation in SDB response according to the nature of the dominant individual, SDB can be used to assess relationship security (i.e. the perceived predictability of a relationship for one partner). Finally, in combination with measures of affiliation rate, SDB may provide insight into relationship value.

Chronic Stress in Dogs Subjected to Social and Spatial Restriction. I. Behavioral Responses

Six weeks of social and spatial restriction were used as a model to induce chronic stress in Beagles. Behavioral and physiological measurements were performed during a period of enriched spacious outdoor housing in groups (GH) and during a subsequent period of solitary housing in small indoor kennels (IH). Behavioral parameters that may indicate chronic stress in dogs are reported. During IH, the dogs showed significantly (comparison-wise error rate <0.05) lower postures than during GH. IH induced enduring increments in frequencies of autogrooming, paw lifting, and vocalizing, and was associated with incidents of coprophagy and repetitive behavior. So far, we interpret the behavioral changes as signs of chronic stress. Relatively low levels of walking, digging, intentions to change from one state of locomotion to another, and increments in circling are conceived as obvious adaptations to the specific features of the IH system. By challenging the dogs outside their home kennel we tested whether the dogs’ coping abilities were affected by IH. Dogs that were challenged were introduced into a novel environment, given the opportunity to escape from their home kennel, restrained, walked down an unfamiliar corridor, presented a novel object, exposed to loud noise, given food, or confronted with a conspecific. During IH, challenged dogs exhibited higher postures, showed more tail wagging, nosing, circling, urinating, and defecating, and changed more often from one state of locomotion (or posture) to another than during GH. These behavioral changes were observed across the different types of challenges, with the exception of the noise administration test. In the presence of conspecifics, the socially and spatially restricted male dogs behaved more dominantly and aggressive than during the time that they were kept in groups. Such behavior manifested as increased performances of raised hairs, growling, paw laying, and standing over. Both sexes showed increases in paw lifting, body shaking, ambivalent postures, intentions to change from one state of locomotion to another, and trembling in any of the challenges, excluding the walking down the corridor test. In short, during a variety of challenges, socially and spatially restricted dogs exhibited a heightened state of aggression, excitement, and uncertainty. Behavioral differences between dogs that had experienced pleasant and bad weather conditions during GH, suggested that “pleasant-weather individuals” had experienced early stress during the control period, and, as a result, responded to the subsequent period of IH differently. Regardless of the housing conditions, challenged bitches showed stronger indications of acute stress than male dogs. Gender did not affect the chronic stress responses to social and spatial restriction. A low posture and increased autogrooming, paw lifting, vocalizing, repetitive behavior, and coprophagy may indicate chronic stress in dogs, and as such, can help to identify poor welfare. When challenged, chronically stressed dogs may show increased excitement, aggression, and uncertainty, but the nonspecificity of such emotional behavior will complicate its practical use with regard to the assessment of stress.

Female fifteen-spined sticklebacks prefer better fathers

We studied how male fifteen-spined sticklebacks,Spinachia spinachia, vary in paternal competence, whether males advertise their competence and whether females prefer better fathers. In this species the male alone provides care for the offspring through nest building, fanning, cleaning and protecting the eggs. We found no female preference for larger males. Instead, females preferred males that during the subsequent paternal phase fanned their nests in shorter fanning bouts. Such males enjoyed a significantly higher hatching success because they fanned more often than males with longer fanning bouts. Males that fanned for short bouts during the paternal phase were also able to increase their fin beat rate. Frequent fanning and high fin beat rates may improve the flow of oxygen to the eggs. Beat rate may be a condition-dependent trait, because males that lost more weight were unable to increase their fin beat rate. During courtship, males perform behaviours such as displacement fanning and body shaking. Females preferred males showing more frequent body shakes during courtship. Body shake frequency correlated positively with hatching success, and negatively with mean fanning bout duration during the paternal phase. The results indicate that femaleS.spinachiashow a preference for direct benefits in terms of better paternal care, and that males may signal this ability to females by shaking their body during courtship.

Behavioural, saliva cortisol and heart rate responses to different types of stimuli in dogs

Stress parameters that can be measured noninvasively may help to identify poor welfare in dogs that live in private homes and institutions. Behavioural parameters are potentially useful to identify stress, but require further investigation to establish which behaviours are appropriate. In the present study, behaviours were recorded and analysed for signs of acute stress in dogs. Simultaneously, saliva cortisol and heart rate were measured to support the interpretation of the behavioural data with regard to stress. Ten dogs of either sex, different ages and various breeds were each subjected to six different stimuli: sound blasts, short electric shocks, a falling bag, an opening umbrella and two forms of restraint. Each type of stimulus had been selected for its assumed aversive properties and was administered intermittently for 1 min. The stimuli that could not be anticipated by the dogs, sound blasts, shocks and a falling bag, tended to induce saliva cortisol responses and a very low posture. The remainder of the stimuli, which were administered by the experimenter visibly to the dog, did not change the cortisol levels but did induce restlessness, a moderate lowering of the posture, body shaking, oral behaviours, and to a lesser extent, yawning and open mouth. Pronounced increases in the heart rate were nonspecifically induced by each type of stimulus. Heart rate levels normalized within 8 min after stressor administration had stopped. Saliva cortisol levels decreased to normal within the hour. Correlations between behavioural and physiological stress parameters were not significant. From the present results, we conclude that in dogs a very low posture may indicate intense acute stress since dogs show a very low posture concomitant with saliva cortisol responses. Dogs may typically show increased restlessness, oral behaviours, yawning, open mouth and a moderate lowering of the posture when they experienced moderate stress in a social setting. The nonspecific character of canine heart rate responses complicates its interpretation with regard to acute stress.

Diagnostic and pathophysiological aspects of psychogenic tremors.

Psychogenic tremor has become a rare movement disorder. Twenty-five patients from our movement disorder unit presented either with obviously nonorganic body shaking during stance or with extremity tremors. A sudden onset and a variable but rarely remitting course of the condition was common. The "coactivation sign of psychogenic tremor" and absent finger tremor were the most consistent criteria to separate them from organic tremors. Quantitative analysis of tremor shows decreasing amplitudes in most organic tremors when the extremity is loaded with additional weights. In contrast, we found an increase of tremor amplitude for most of the cases with psychogenic tremor. This might be caused by increased coactivation to maintain the oscillation. These clinical and electrophysiological features suggest a clonus mechanism induced by coactivation as the pathophysiological basis of psychogenic extremity tremor. Psychiatric evaluation did not show overt signs of hysteria for the majority of the patients. However, we found depression and functional somatic or psychosomatic conditions to be frequent among the patients. A reduced ability to cope with stressful situations may play a significant role. The clinical course of the condition is usually far from benign. We conclude that psychogenic tremor can be positively diagnosed by means of neurologic signs in the majority of patients and is not only a diagnosis of exclusion. The poor outcome makes early and serious neuropsychiatric attempts at therapy necessary.

Differences in responses to propofol in elderly and young adult WISW rats

How elderly and young adults differ in their susceptibility to propofol, a GABA-mimetic drug, was studied in WISW rats. The incidence of narcosis (4–20 mg/kg) or in the potency of propofol to inhibit withdrawal reflexes (ED50: 1.2 mg/kg) did not differ, but narcosis lasted longer (20 mg/kg: 25 min v. 17 min), and both the onset (t1/2: 0.7 min v. 0.3 min) and decay (t1/2: 16 min v. 7 min) of reflex inhibition were slower in elderly than in young adults. Moreover, propofol-induced behavior differed: tail flicks, head and body shakes and walking difficulties occurred less frequently, whereas vacuous chewing occurred more often in elderly than in young adult rats. In all, age-dependent difference in the potency of propofol show in susceptibility for certain side-effects and these may relate to rapidity of effect and GABA functionality in the brain. © 1997 John Wiley & Sons, Ltd.

Effect of Adenosine Receptor Agonists and Antagonists on the Expression of Opiate Withdrawal in Rats

The effects of the selective A 1 adenosine receptor agonist N 6-cyclopentyladenosine (CPA) and the selective A 2a agonist 2-[p-(2-carboxethyl)phenylethyl-ethylamino]-5′-ethylcarboxamidoadenosine (CGS 21680) (each at 0.03, 0.1 and 0.3 mg/kg, SC) as well as the selective A 1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), non-selective antagonists 3-isobutyl-1-methylxanthine (IBMX), aminophylline, 3,7-dimethyl-1-propargyl-xanthine (DMPX) and 8(p-sulfophenyl)-theophylline (8-SPT) were investigated (each at 5, 10 and 30 mg/kg, SC) for their ability to alter the naloxone-precipitated opiate withdrawal syndrome in morphine-dependent rats. Effects of CPA and CGS 21680 on opiate withdrawal in the presence of aminophylline were also investigated. Both CPA and CGS 21680, caused a significant reduction in the incidence of body shakes, teeth chatter and paw shakes and decreased the amount of faecal matter produced. DPCPX, IBMX, DMPX, 8-SPT and aminophylline significantly increased the incidence of jumps and decreased the amount of faecal matter produced. The incidence of body shakes was significantly increased by DMPX, 8-SPT and IBMX. Neither CPA nor CGS 21680 were able to reverse the significant increase in the incidence of jumps caused by aminophylline. These data suggest that there is a role for endogenous adenosine in the modulation of the opiate abstinence syndrome and both A 1 and A 2a adenosine receptors are involved in this phenomenon.

Involvement of δ 1 and δ 2 Opioid Receptor Subtypes in the Development of Physical Dependence on Morphine in Mice

The effects of the highly selective δ opioid receptor antagonists naltrindole (NTI) for δ 1 and δ 2 naltriben (NTB) and naltrindole 5′-isothiocyanate (5′-NTII) for δ 2 and 7-benzylidenenaltrexone (BNTX) for δ 1 on the development of physical dependence on morphine were investigated in mice. Neither NTI (3 mg/kg, sc), NTB (0.5 mg/kg, sc), 5′-NTII (0.5 mg/kg, sc) nor BNTX (0.5 mg/kg, sc) suppressed the antinociception induced by morphine (10 mg/kg, sc). Pretreatment with NTI (3 mg/kg, sc), NTB (0.5, 1.0 mg/kg, sc) or 5′-NTII (0.5, 1.0 mg/kg, sc) during chronic treatment with morphine for 5 days significantly suppressed naloxone-induced body-weight loss in morphine-dependent mice. The incidence of jumping and body shakes in morphine-dependent mice that were pretreated with NTI, NTB or 5′-NTII were significantly lower than with morphine alone. Pretreatment with BNTX (0.5, 1.0 mg/kg, sc) during chronic treatment with morphine also significantly suppressed naloxone-induced body-weight loss in morphine-dependent mice, but this suppression was weaker than that by the antagonists. In contrast to mice that had been pretreated with NTI, NTB or 5′-NTII, the incidence of several withdrawal signs, such as jumping and body shakes, was not significantly affected in morphine-dependent mice that were pretreated with BNTX. These findings suggest that both δ 2 and δ 1 opioid receptors may play important roles in modulating the development of physical dependence on morphine.

Effect of Intrathecal Pretreatment With the Neurokinin Receptor Antagonist CP-99994 on the Expression of Naloxone-Precipitated Morphine Withdrawal Symptoms

In morphine-dependent rats pretreated with an intrathecal injection of saline (vehicle), intraarterial injection of 0.5 mg/kg of naloxone produced an immediate increase in blood pressure. Heart rate increased in most rats just after naloxone injection; however, the responses were transient, not lasting more than about 4 min after injection. Naloxone-precipitated behavioral changes were dominated by the appearance of body shakes and escape attempts that were strongly expressed during the first 10 min after naloxone. Pretreatment of morphine-dependent rats with an intrathecal injection of 100 nmol of the neurokinin-1 receptor antagonist CP-99994 significantly inhibited the magnitude and shortened the duration of the pressor response to naloxone. CP-99994 did ot reduce the expression of the associated withdrawal behaviors. Substance P significantly reversed the inhibitory effects of CP-99994 on the expression of the withdrawal-associated pressor response. Intrathecal pretreatment with CP-99994 also produced a dose-dependent inhibition of the expression of the pressor response to local spinal (intrathecal) injection of naloxone (60 micrograms) in morphine dependent rats without significant alteration of the expression of withdrawal-associated behaviors. These results indicate that spinal neurokinin-1 receptors mediate some of the cardiovascular signs of morphine withdrawal and suggest the possibility of developing a novel class of antiopiate withdrawal agents.

Antibodies directed against the mu-opioid receptor alleviated multiple signs of morphine withdrawal in mice

An investigation was made into the effect of intracerebroventricular (i.c.v.) administration of antibodies to the amino-terminal portion 1–16 (MDSSTGPGNTSDCSDP) or the peptide sequence 208–216 (TKYRQGSID) of the cloned μ-opioid receptor (μ-OR) on morphine tolerance and dependence. Animals were rendered tolerant-dependent by subcutaneous (s.c.) implantation of an oily morphine suspension. To precipitate withdrawal syndrome, the opioid antagonist naloxone (1 mg kg , s.c.) was administered 72 h after chronic morphine treatment. In mice i.c.v. injected with the anti-μ-OR antibodies, the analgesic effect of chronic morphine was significantly reduced. These antibodies given 24 h before starting the chronic morphine treatment, reduced most of the symptoms associated with the withdrawal syndrome (jumps, loss of body weight, diarrhoea and body shakes) elicited by naloxone in dependent mice. The administration of the antisera to mice undergoing 48 h of chronic morphine treatment did not precipitate detectable signs of abstinence, but reduced the withdrawal syndrome precipitated by naloxone 24 h later. The finding that both antibodies impaired μ 1 μ 2 - mediated effects, suggests a high degree of homology between the pharmacologically defined subtypes of μ-OR.

P-13-1 - Saccadic eye movements in gilles-de-la-tourette-syndrome

Cocaine (5–40 mg/kg, intraperitoneally) enhanced locomotion and rearing accompanied with head circling and body shaking. Although at 40 mg/kg typical stereotypy licking occasionally appeared, 40% of the rats died. At doses that did not affect physiologic locomotion and rearing, the D1-receptor antagonist SCH23390 but not D2 antagonist raclopride inhibited locomotion and rearing stimulated by cocaine (20 mg/kg). All behavioral responses of cocaine were abolished with increasing doses of raclopride and SCH23390. Sulpiride, a D2 antagonist, exerted a biphasic effect on locomotor activity (i.e., a low dose of sulpiride increased and a high dose decreased cocaine-induced locomotor activity). Sulpiride enhanced head circling, body shaking, and increases of rearing induced by cocaine. D2-receptor agonists quinpirole and bromocriptine inhibited these responses, presumably by activating the typical stereotyped behaviors such as sniffing at low doses, and licking and gnawing at high doses. The lowest dose of bromocriptine inhibited all behaviors induced by cocaine without producing typical stereotyped behaviors in itself. SK&F38393, a D1-receptor agonist, in combination with cocaine did not induce typical stereotypy, which results in a synergistic effect of D1 and D2-receptor activities. The increases of locomotion and rearing, head circling, and body shaking induced by cocaine may involve the indirect activation of postsynaptic D1 and D2 receptors, presumably via dopamine release, resulting from inhibition of the presynaptic D2 receptors. These results also provide evidence that the indirect stimulation of postsynaptic D2 receptors by cocaine (20 mg/kg) is insufficient to induce stereotyped behaviors, and that the role of dopamine D1 receptors in mediating the behavioral actions of acute cocaine appears to be more important than that of D2 receptors. Our results also suggest that bromocriptine may be useful for the treatment of acute cocaine poisoning.

Primate displacement activities as an ethopharmacological model of anxiety.

Using a within-subject cross-over, vehicle-controlled design, we investigated the acute effects of benzodiazepine receptor ligands with different mechanisms of action on the displacement activities (scratching, self-grooming, and body shake) of seven male macaques living in social groups. Our aim was to test the discriminative validity of displacement activities as an ethopharmacological model of anxiety. Subjects were given i.m. lorazepam (0.10, 0.20, 0.25 mg/ kg) and FG 7142 (0.1, 0.3, 1.0 mg/kg). The frequency of displacement activities was decreased by the anxiolytic lorazepam and increased by the anxiogenic FG 7142 in a dose-dependent manner. Displacement activities were apparently more sensitive to anxiolytic treatment than other behavior patterns indicative of an anxiety state (i.e., visual scanning of the social environment and fear responses directed to dominant males). These results suggest that primate displacement activities are a valid ethopharmacological model of anxiety.

Involvement of D 1 and D 2 dopamine systems in the behavioral effects of cocaine in rats

Cocaine (5–40 mg/kg, intraperitoneally) enhanced locomotion and rearing accompanied with head circling and body shaking. Although at 40 mg/kg typical stereotypy licking occasionally appeared, 40% of the rats died. At doses that did not affect physiologic locomotion and rearing, the D 1-receptor antagonist SCH23390 but not D 2 antagonist raclopride inhibited locomotion and rearing stimulated by cocaine (20 mg/kg). All behavioral responses of cocaine were abolished with increasing doses of raclopride and SCH23390. Sulpiride, a D 2 antagonist, exerted a biphasic effect on locomotor activity (i.e., a low dose of sulpiride increased and a high dose decreased cocaine-induced locomotor activity). Sulpiride enhanced head circling, body shaking, and increases of rearing induced by cocaine. D 2-receptor agonists quinpirole and bromocriptine inhibited these responses, presumably by activating the typical stereotyped behaviors such as sniffing at low doses, and licking and gnawing at high doses. The lowest dose of bromocriptine inhibited all behaviors induced by cocaine without producing typical stereotyped behaviors in itself. SK&F38393, a D 1-receptor agonist, in combination with cocaine did not induce typical stereotypy, which results in a synergistic effect of D 1 and D 2-receptor activities. The increases of locomotion and rearing, head circling, and body shaking induced by cocaine may involve the indirect activation of postsynaptic D 1 and D 2 receptors, presumably via dopamine release, resulting from inhibition of the presynaptic D 2 receptors. These results also provide evidence that the indirect stimulation of postsynaptic D 2 receptors by cocaine (20 mg/kg) is insufficient to induce stereotyped behaviors, and that the role of dopamine D 1 receptors in mediating the behavioral actions of acute cocaine appears to be more important than that of D 2 receptors. Our results also suggest that bromocriptine may be useful for the treatment of acute cocaine poisoning.

Involvement of β-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and α-melanocyte-stimulating hormone, in rats

The present study was undertaken to investigate whether β-adrenoceptors are involved in regulation of yawning responses to oxytocin and α-melanocyte-stimulating hormone (α-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. α-MSH (20 μg/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M 1 receptor agonist, administered ICV at a lower dose of 100 μg/rat and subcutaneously (SC) at doses of 0.25–2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a β-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by α-MSH (20 μg/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH 2) 5,Tyr(Me) 2,Orn 8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, α-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a muscarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D 2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and α-MSH is modulated by β-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M 1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.

Alteration of D1 and D2 dopaminergic receptor kinetics in specific rat brain regions following repeated administration of opiates.

The present study was conducted to investigate the effects of repeated administration of opiates on the binding characteristics of D1 and D2 dopamine receptors in specific rat brain regions. Male Sprague-Dawley rats (150-175 g) were adapted for 1 week under controlled conditions (22 +/- 1 degree C, 40% relative humidity, 12 h light:12 h dark illumination cycle). After the adaptation period, rats were randomly assigned into six groups (n = 15/group) for two sets of experiments; one for D1 and the other for D2 receptor binding evaluation. In each set, group 1 served as saline control, group 2 was treated with morphine (1 mg/kg/day for 7 days) and group 3 was treated with naloxone (2 mg/kg/day for 7 days). Following the third day of morphine injection, rats showed restlessness, hyperactivity, increased urination, diarrhea, lacrimation, irritability and squealing on touch, head and body shakes and salivation just prior to morphine dosage. These observed signs are typical for morphine withdrawal. One hour after the last injection, rats were sacrificed by decapitation, brains were removed and kept at -70 degrees C. The frozen brains were further dissected into cortex (CTX), hypothalamus (HYPO), hippocampus (HIPP) and midbrain (MID), pooled (5/pool), homogenized and used for radioreceptor assays. For D1 binding study, 3H-SCH-23390 was used as ligand and for D2 receptor binding 3H-YM-09151-2 was employed. Following repeated morphine or naloxone treatment, Bmax values for 3H-SCH-23390 binding to membranes of HYPO and MID were increased and decreased, respectively, whereas Kd values were significantly decreased in both HYPO and MID of morphine and naloxone-treated animals. In rat brain CTX, both morphine and naloxone decreased Kd and Bmax values of 3H-SCH-23390 binding, however the decrease in Bmax values noted after morphine administration was not statistically significant. Decrease in both Bmax and Kd values of dopamine D1 receptors were observed after naloxone but not morphine treatment in HIPP. Morphine administration increased the density of D2 receptors in HIPP and MID and decreased the affinity of 3H-YM-09151-2 binding in CTX, HIPP and MID. Naloxone treatment resulted in increased number of 3H-YM-09151-2 binding sites in CTX, HYPO and HIPP. While naloxone treatment increased Kd values of 3H-YM-09151-2 in HYPO and HIPP, it decreased these values in CTX and MID. It is concluded that repeated intermittent treatment with opiates induces alterations in D1 and D2 dopamine receptors binding properties and that these changes are regionally specific.(ABSTRACT TRUNCATED AT 400 WORDS)