Stretch Attend Research Articles

Chemical analysis of calabash chalk and its effect on locomotor activities and behavior in Swiss albino mice

Continuous exposure of young women to calabash chalk, especially at child-bearing age, necessitated this study to analyze the chemical constituents of calabash chalk and to evaluate its effect on locomotor activities and behavior in Swiss albino mice. Dried cubes of calabash chalk were purchased and analyzed by atomic and flame atomic absorption spectrophotometer. Twenty-four Swiss-albino mice were taken and divided into four groups: control (1 ml distilled water) and three treated groups with the doses of 200 mg/kg, 400 mg/kg, and 600 mg/kg of calabash chalk suspension, respectively, by oral gavage. Hole Cross, Hole Board, and Open Field tests were performed to evaluate the locomotor activities, behavior, and anxiety along with measurement of body weight. The data were analyzed by SPSS-software. Chemical analysis of calabash chalk showed the presence of trace elements along with some heavy metals such as lead (19.26 ppm), Chromium (34.73 ppm), and arsenic (4.57 ppm). After 21 days of oral administration of calabash chalk, the study showed a significant decrease in body weight in the treated groups of mice (p < 0.01). Decreased locomotor activities were also observed in all three experiments. Significantly decreased locomotion and behaviors were also observed in the hole crossing, line crossing, head dipping, grooming, rearing, stretch attend, central square entry, central square duration, defecation, and urination, in a dose-dependent manner (p < 0.01). These effects also prove the anxiogenic behavior of calabash chalk in albino mice. Heavy metals are believed to be harmful to the brain and responsible for cognitive dysfunction and elevated anxiety. In this study, decreased body weight in mice may occur due to disorders in hunger and thirst centers of the brain by heavy metals. Therefore, heavy metals may be responsible for muscle weakness, decreased locomotor activities, and axiogenic effects of mice.

Involvement of the ventral, but not dorsal, hippocampus in anxiety-like behaviors in mice exposed to the elevated plus maze: participation of CRF1 receptor and PKA pathway.

The hippocampus is a limbic structure involved in anxiety-like behaviors. We aimed to evaluate the role of the dorsal (DH) and ventral (VH) hippocampus in anxiety-like behaviors in the elevated plus maze (EPM). We inhibited these brain regions using cobalt chloride (CoCl2: 1.0nmol) microinjections. We also investigated the involvement of corticotropin-releasing factor (CRF) action and protein kinase A (PKA) pathway using intra-DH and intra-VH microinjections of the CRF1 receptor antagonist CP376395 (0, 3.0, or 6.0nmol) and the PKA inhibitor H-89 (0, 2.5, or 5.0nmol). The results indicated that intra-VH CoCl2 microinjection increased the percentage of time spent and entries in the open arms. The mice also exhibited fewer stretch attend postures in the protected area and increased percentage of open arm entries. Further, intra-VH injection of 3.0nmol CP376395 increased time spent in the open arms. Intra-DH injection of 6.0nmol CP376395 increased the frequency of unprotected head dipping, whereas intra-VH injection of 6nmol CP376395 increased the frequency of protected head dipping. Intra-VH, but not intra-DH, microinjection of 2.5nmol H-89 increased the percentages of open arm entries and time spent in the open arms. Microinjection of 2.5 and 5.0nmol H-89 reduced the frequency of protected head dipping behavior. This study demonstrated that VH modulates anxiety-like behaviors in EPM. Moreover, CRF and the cAMP/PKA pathway seem to modulate these effects.

Defensive behaviors and brain regional activation changes in rats confronting a snake

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

Acute Administration of Nymphaea lotus Increases Body Weight and Exploratory Behaviour in Mice

Background and Aim: The effects on body weight and exploratory behavior following acute administration of the leaves of Nymphaea lotus were determined using mice as experimental animals. Methods: Thirty Swiss white mice were randomly divided into group A, B and C. All the mice had access to clean drinking water ad libitum. Before the neurobehavioral parameters were assessed, the LD50 and the phytochemical screening of the leaves of the plant were determined. The open field maze and the light/dark transition box apparatus were used to determine the level of exploratory behaviors in mice. Results: In the open field maze, the line crosses and rearing frequency were significantly different when compared to control (P<0.01). Stretch Attend Posture frequency (SAP) was significantly higher in the test groups when compared to control (P<0.01). It was also observed that the frequency of grooming in the light/dark transition box decreased in the treated groups when compared to the control group (P<0.05 and at P<0.01). Frequency of transition were significantly higher (P<0.01 and at P<0.001) compared to control. The body weight was significantly higher in the mice treated groups when compared to control (P<0.01). Conclusion: Thus, the leaves of Nymphaea lotus enhances exploratory behavior and increases body weight in mice.

Age and sex regulate kappa opioid receptor-mediated anxiety-like behavior in rats

Anxiety occurs across ontogeny, but there is evidence that its etiology may vary across the lifespan. The kappa opioid receptor (KOR) system mediates some of the anxiogenic effects of stress and drug exposure, and is involved in aversive responses to environmental stimuli. However, much of this work has been conducted in adult males. Work assessing the effects of KOR activation in younger males has demonstrated that this system produces an anxiolytic/no response, indicating that that this system may be developmentally regulated. Despite these discrepancies, a direct comparison of KOR-induced anxiety in stress-naïve adolescents and adults has not been done. Additionally, the effects of KOR activation in females are poorly understood. Therefore, we assessed the impact of KOR activation on anxiety-like behavior in adolescent and adult male and female Sprague-Dawley rats. Animals were given an i.p. injection of the KOR agonist U69593 (0.01, 0.1, 1.0 mg/kg or vehicle) and were tested using the elevated plus maze. U69593 decreased open arm time in adult males, indicating increased anxiety-like behavior. Adolescents exhibited decreased stretch attend postures when collapsed across sex, suggesting reduced anxiety-like behavior. Adult females were not affected by U69593 administration. These data support studies that have identified age-dependent changes in the KOR system in males, and provide novel evidence that females may not exhibit this ontogenetic change. Given the prevalence of stress and drug exposure during the adolescent period, differences in how the KOR system may mediate the effects of these exposures across age and sex should be explored.

Anxiolytic and Antidepressant Effects of Maerua angolensis DC. Stem Bark Extract in Mice.

Introduction The stem bark extract of Maerua angolensis DC. (Capparaceae) is used as a traditional remedy for management of anxiety, psychosis, and epilepsy. Aim of the Study We therefore aimed at evaluating the anxiolytic and antidepressant potential of the plant in mice models. Methods The dried stem bark was extracted with petroleum ether/ethyl acetate (50:50) mixture to obtain the extract, MAE. We employed Irwin's test to identify the preliminary behavioral and autonomic effects. Subsequently, MAE was administered per os to male mice and subsequently assessed, 1 h later, for anxiety parameters in the elevated plus maze (EPM) and the regular Suok tests. The forced swim (FST) and tail suspension (TST) tests were employed to assess the antidepressant potential of the extract (100-1000 mg kg−1). Results In our preliminary assay, MAE (100-5000 mg/kg) exhibited analgesic effects and a reduction in fear response in the Irwin's test. The spontaneous locomotor activity was reduced at 1000 mg/kg. Additionally, MAE (1000 mg/kg) increased the latency to PTZ-induced convulsions, and duration to sleep in the pentobarbitone induced sleeping time assay. MAE (1000 mg/kg), similar to diazepam, in the anxiolytic assay, increased the percentage time spent in the open arms while decreasing protected head dips and unprotected stretch attend postures in the EPM. Correspondingly, there was a reduction in anxiety-induced immobility and freezing in the Suok test (300 mg/kg) without loss of sensorimotor coordination. Additionally, there was a significant reduction in immobility duration in the FST (300 mg/kg) and TST (1000 mg/kg). Conclusion The petroleum ether/ethyl acetate fractions of Maerua angolensis stem bark possess anxiolytic and acute antidepressant effects in mice.

A Novel Integrative Mechanism in Anxiolytic Behavior Induced by Galanin 2/Neuropeptide Y Y1 Receptor Interactions on Medial Paracapsular Intercalated Amygdala in Rats.

Anxiety is evoked by a threatening situation and display adaptive or defensive behaviors, found similarly in animals and humans. Neuropeptide Y (NPY) Y1 receptor (NPYY1R) and Galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the amygdala. In a previous study, GALR2 enhanced NPYY1R mediated anxiolytic actions on spatiotemporal parameters in the open field and elevated plus maze, involving the formation of GALR2/NPYY1R heteroreceptor complexes in the amygdala. Moreover, the inclusion of complementary ethological parameters provides a more comprehensive profile on the anxiolytic effects of a treatment. The purpose of the current study is to evaluate the anxiolytic effects and circuit activity modifications caused by coactivation of GALR2 and NPYY1R. Ethological measurements were performed in the open field, the elevated plus-maze and the light-dark box, together with immediate early gene expression analysis within the amygdala-hypothalamus-periaqueductal gray (PAG) axis, as well as in situ proximity ligation assay (PLA) to demonstrate the formation of GALR2/NPYY1R heteroreceptor complexes. GALR2 and NPYY1R coactivation resulted in anxiolytic behaviors such as increased rearing and head-dipping, reduced stretch attend postures and freezing compared to single agonist or aCSF injection. Neuronal activity indicated by cFos expression was decreased in the dorsolateral paracapsular intercalated (ITCp-dl) subregion of the amygdala, ventromedial hypothalamic (VMH) nucleus and ventrolateral part of the periaqueductal gray (vlPAG), while increased in the perifornical nucleus of the hypothalamus (PFX) following coactivation of GALR2 and NPYY1R. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was explicitly observed in ITCp-dl, following GALR2 and NPYY1R coactivation. Besides, knockdown of GALR2 was found to reduce the density of complexes in ITCp-dl. Taken together, these results open up the possibility that the increased anxiolytic activity demonstrated upon coactivation of NPYY1R and GALR2 receptor was related to actions on the ITCp-dl. GALR2-NPYY1R heteroreceptor complexes may inhibit neuronal activity, by also modifying the neuronal networks of the hypothalamus and the PAG. These results indicate that GALR2/NPYY1R interactions in medial paracapsular intercalated amygdala can provide a novel integrative mechanism in anxiolytic behavior and the basis for the development of heterobivalent agonist drugs targeting GALR2/NPYY1R heteromers, especially in the ITCp-dl of the amygdala for the treatment of anxiety.

Evaluation of the anxiolytic activity of the leaves of Nymphaea lotus (Water Lily) in mice.

The anxiolytic effect of the leaves of water lily was investigated using mice as experimental animals. Thirty (30) were mice randomly divided into group 1, 2 and 3. Before the neurobehavioral parameters were assessed, the LD50 and the phytochemical screening of the leaves of the plant were determined. The open field maze and the transition box apparatus were used to determine the level of fear and anxiety related behaviors in mice. In the open field arena, the grooming frequency was statistically not different when compared to control. Stretch attend posture frequency (SAP) was statistically higher in the test groups when compared to control (P<0.001). It was also observed that the frequency of defecation decreased in the treated groups when compared to the control group (P<0.01). The light duration box and frequency of transition were statistically higher (P<0.001) compared to control. Thus, the leaves of the plant tend to reduce the level anxiety in mice.

The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats.

Introduction:This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats.Methods:The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test.Results:Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001).Conclusion:Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects.

The effect of administration of amodiaquine on some Parameters of neurobehaviour of wistar rats

The effect of administration of amodiaquine (AQ) on some parameters of neurobehaviour of Wistar rats was carried out. Twenty adult Wistar rats weighing between 160-190g were divided equally into four groups. Group 1 served as the control, while groups 2, 3 and 4 were the experimental groups. The control group received distilled water. Groups 2 and 3 were treated with 8.75mg/kg and 17.50mg/kg respectively of amodiaquine for three days, while group 4 was treated with 8.75mg/kg of AQ for six days. Neurobehaviour test using the open field was carried out twelve hours after the last administrations. There were no significant differences between the control and the experimental groups in total locomotor activity (TLA), central square duration (CSD), stretch-attend (SA) and defecation. In the central square frequency (CSF), group 3 was significantly [P < 0.05] higher than all the groups, while the control was the same as group 4, but higher than group 2, with the difference not being significant. In conclusion, amodiaquine increased TLA and exploration, while simultaneously reducing anxiety in Wistar rats and these were dose dependent.

Systematic analysis of emotionality in consomic mouse strains established from C57BL/6J and wild‐derived MSM/Ms

Consomic strains have recently attracted attention as an advantageous method to screen for genes related to developmental, physiological, and behavioral phenotypes. Recently, a new set of consomic strains was established from the Japanese wild-derived mouse strain MSM/Ms and C57BL/6JJcl. By analyzing the entire consomic panel, we were able to identify a number of chromosomes associated with anxiety-like behaviors in the open-field (OF) test, a light–dark box and an elevated plus maze. Detailed observation of the OF behavior allowed us to identify chromosomes associated with those ethological traits, such as stretch attend, rearing, and jumping. Repeated OF test trials have different meanings for animals, and we found that some chromosomes responded to only the first or second trial, while others were consistent across both trials. By examining both male and female mice, sex-dependent effects were found in several measurements. Principal component analysis of anxiety-like behaviors extracted five factors: ‘general locomotor activity’, ‘thigmotaxis’, ‘risk assessment’, ‘open-arm exploration’ and ‘autonomic emotionality’. We mapped chromosomes associated with these five factors of emotionality.

Effects of intra-PAG infusion of ovine CRF on defensive behaviors in Swiss-Webster mice

The midbrain dorsal periaqueductal gray (DPAG) is part of the brain defensive system involved in active defense reactions to threatening stimuli. Corticotrophin releasing factor (CRF) is a peptidergic neurotransmitter that has been strongly implicated in the control of both behavioral and endocrine responses to threat and stress. We investigated the effect of the nonspecific CRF receptor agonist, ovine CRF (oCRF), injected into the DPAG of mice, in two predator–stress situations, the mouse defense test battery (MDTB), and the rat exposure test (RET). In the MDTB, oCRF weakly modified defensive behaviors in mice confronted by the predator (rat); e.g. it increased avoidance distance when the rat was approached and escape attempts (jump escapes) in forced contact. In the RET, drug infusion enhanced duration in the chamber while reduced tunnel and surface time, and reduced contact with the screen which divides the subject and the predator. oCRF also reduced both frequency and duration of risk assessment (stretch attend posture: SAP) in the tunnel and tended to increase freezing. These findings suggest that patterns of defensiveness in response to low intensity threat (RET) are more sensitive to intra-DPAG oCRF than those triggered by high intensity threats (MDTB). Our data indicate that CRF systems may be functionally involved in unconditioned defenses to a predator, consonant with a role for DPAG CRF systems in the regulation of emotionality.

Repetitive acute pain in infancy increases anxiety but does not alter spatial learning ability in juvenile mice

We assessed the long-term behavioural effects of a single acute or repetitive inflammatory pain experienced during infancy. Groups of male and female CD1 mice were subjected to either an acute single pain, i.e. a tail clip or sham pain at P8, or acute repetitive pain in the form of needle pricks or sham pain from P8 to P14. All of the subjects were tested in the elevated plus maze at P30 and in the Morris Water Maze from P31 to P38. Mice in the acute single pain and sham groups did not differ on measures of anxiety in the plus maze. Mice in the repetitive pain group demonstrated significantly more anxious behaviours than controls in the elevated plus maze as they spent less time in the open arms, made fewer open arm entries, displayed fewer head dips and showed more stretch attend postures. There were no effects of single or repetitive pain treatments in the latency to find the hidden platform in the Morris Water Maze. Overall, these data suggest that acute repetitive pain experienced during infancy may increase anxiety later in life but it does not influence spatial learning as measured in the Morris Water Maze. The origin of the anxiogenic profile shown in the acute repetitive pain mice may be a result of changes in neural circuitry or context dependent learning and is currently under further investigation with this paradigm.

Infralimbic D2 receptor influences on anxiety-like behavior and active memory/attention in CD-1 mice

Ventromedial prefrontal cortical (vmPFC) dopamine (DA) influences attentional aspects of cognition and anxiety-like behavioral responding in rodents. The present study investigated the role of D2 receptors on spontaneous alternation in the Y-maze and anxiety-like behavior in a two-trial elevated plus-maze (EPM) procedure in CD-1 mice following vmPFC infusions of the D2 antagonist, sulpiride, and the D2 agonist, quinpirole. Pretrial 1 quinpirole infusions did not influence any anxiety measure (with the exception that the lowest dose increased protected stretch attends), but reduced protected exploration activity (closed-arm entry/time ratios and wall rearing). In Trial 2 24 h later (no injection), quinpirole exerted an anxiolytic behavioral profile relative to Trial 2 control mice (enhanced open-arm entry/time ratios, unprotected head dips), with no effects on protected exploration or risk assessment activity. Pretrial 1 sulpiride infusions enhanced unprotected exploration (open-arm entry/time ratios, unprotected stretch attend, and head dips), but did not influence protected exploration or risk assessment in the EPM. In Trial 2, 24 h later (no injection), sulpiride extended this anxiolytic profile to reduced protected exploration and risk assessment activity (closed-time ratio, protected stretch attend, and head dips). In the Y-maze, whereas quinpirole disrupted alternation performance (5- and 10-nmol dose) concomitant with marked repetitive same-arm returns (SAR) at the highest dose, sulpiride disrupted alternation performance concomitant with marked repetitive SAR behavior at the lowest dose only. These data indicate that although infralimbic (IL) quinpirole and sulpiride infusions similarly disrupted alternation performance in the Y-maze and reduced Trial 2 anxiety-like responding in the EPM, these drugs differentially produced these effects.

Cue and context conditioning of defensive behaviors to cat odor stimuli

Exposure of rats to a cat odor block in a previously familiarized situation was followed by three extinction days to the same or a different situation, and with or without an identical but odor-free block, and, testing in the original apparatus with an odor-free block (cue). Initial exposure produced risk assessment (stretch attend), avoidance of the block, and crouch/freeze with sniffing/head movements. Avoidance continued during extinction, but context-only exposed rats showed predominantly crouch/freeze with sniff/head movements, while rats exposed to the context+cue showed higher levels of stretch attend. During the test day, rats exposed to the cue during extinction showed reduced defensive responding compared to those not extinguished with the cue, but context extinction had less effect, possibly due in part to initial familiarization with the situation.These data indicate that both cue and context conditioning to cat odor did occur, and that the type of conditioned stimulus (context-only vs. context+cue) influenced the type of defensive behaviors elicited by this stimulus, although the all animals received the same conditioning protocol. Particular behaviors disappeared at different rates during extinction, with avoidance the most persistent. However, in this context there was no incentive for approach behaviors inconsistent with avoidance, and stretch attend behaviors could and did occur while subjects were located far from the block or the area in which it had been encountered. In addition, immobile crouch/freeze did not occur at higher than control levels, while the crouch/freeze activities that did increase incorporated sensory sampling in a relevant modality (sniffing/head movements). Thus, the behaviors seen to the conditioned stimulus appeared to reflect combinations of different defense strategies, appropriate to the type of conditioned stimulus and responsive to its extinction. Differences between these data and those from studies using fecal predator odorants suggest that the latter may not elicit a complete range of conditioned defenses.

A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field

The open field test (OFT) is a widely used procedure for examining the behavioral effects of drugs and anxiety. Detailed ethological assessments of animal behavior are lacking. Here we present a detailed ethological assessment of the effects of acute treatment with the benzodiazepines, diazepam (DZ, 1.5 mg/kg) and chlordiazepoxide (CDP, 5.0 and 10.0 mg/kg), as well as exposure to a non-pharmacological agent, a specific pulsed extremely low frequency magnetic field (MAG) on open field behavior. We examined the duration, frequency and time course of various behaviors (i.e. exploration, walk, rear, stretch attend, return, groom, sit, spin turn, jump and sleep) exhibited by male mice in different regions of a novel open field. Both DZ and CDP consistently reduced the typical anxiety-like behaviors of stretch attend and wall-following (thigmotaxis), along with that of an additional new measure: ‘returns’, without producing any overall effects on total locomotion. The drugs also differed in their effects. CDP elicited a shift in the locomotor pattern from a ‘high explore’ to a ‘high walk’, while DZ mainly elicited alterations in sit and groom. The MAG treatment was repeated twice with both exposures reducing horizontal and vertical (rearing) activity and increasing grooming and spin turns. However, the anxiety-like behaviors of stretch attend and return were marginally reduced by only the first exposure. We conclude that a detailed ethological analysis of the OFT allows not only the detection of specific effects of drugs and non-pharmacological agents (i.e. pulsed magnetic field) on anxiety-like behaviors, but also permits the examination of non-specific effects, in particular those on general activity.

Amygdala Lesions Produce Analgesia in a Novel, Ethologically Relevant Acute Pain Test

Acute pain tests using mechanical stimuli typically do not involve objects important in the evolutionary history of the subjects, and may fail to evaluate the contribution of biobehavioral defensive reactions to the total pain response. Spines are common structural defenses that protect plants and animals against predation. The present studies examined the reaction to contact with such natural, mechanical pain stimuli in the laboratory rat, utilizing a floor board with protruding pins located in the middle of a novel alley (the “fakir” test). Behavioral responses were characterized in 10-min tests (Experiment 1). Subjects showed voluntary contact with the pins followed by patterns of avoidance and risk assessment (stretch attend and stretch approach). Few subjects crossed the array of pins. The amygdala has been implicated in the perception of pain, particularly in stressful or fearful contexts. In Experiment 2, the fakir test was used to examine, concurrently, the effects of amygdala lesions on analgesiometric (frequency and duration of pin crossings) and anxiometric (risk assessment) measures. Large, bilateral, lesions of the amygdala significantly increased both the number of pin crossings and time spent on the pins without affecting the risk assessment measures. These findings suggest a possible dissociation between anxiety and pain perception with an important (nonaffective) role for the amygdala in the latter.

8-OH-DPAT in the median raphe nucleus decreases while in the medial septal area it may increase anxiety in female rats

The experiment evaluated the effects of 8-OH-DPAT on the activity of virgin female rats (diestrus) in the elevated plus maze. The 5-HT 1A receptor agonist was infused into the median raphe nucleus ( N=60) and medial septal area ( N=68) 10 min before the test. Five groups for each brain area were analyzed: intact, saline (0.2 μl) and 8-OH-DPAT (0.2; 0.5 and 2.0 μg rat −1). The following measures were recorded: number of entries onto open and enclosed arms and time spent on the open and enclosed arms. In addition, the frequency of stretch–attend and head-dipping were also evaluated. The results showed that in the median raphe nucleus only the highest dose of 8-OH-DPAT (2.0 μg) increased the percentage of time spent on the open arms. On the other hand, in medial septal area 8-OH-DPAT in the dose of 0.5 μg decreased the percentage of time spent on the open arms, while the doses of 0.2 and 2.0 μg had no significant impact on anxiety. Data suggest that 8-OH-DPAT acting on 5-HT 1A somatodendritic autoreceptors decreases anxiety. However, at a specific dosage and acting on postsynaptic receptors of the medial septal area, 8-OH-DPAT can increase anxiety.

The ontogeny of exploratory behaviors in early-protein-malnourished rats exposed to the elevated plus-maze test

An elevated plus-maze was used to study the ontogeny of the exploratory behaviors of early-protein-malnourished animals in an experimental aversive situation. Rats were malnourished by feeding their dams a 6% protein diet during the lactation period (0–21 days of age); controls received a 16% protein diet. From 21 to 100 days of age, all rats received a balanced lab chow diet. At 21, 30, 40, 50, 60, 70, 80, 90, and 100 days of age, independent groups of malnourished and control animals were exposed to the elevated plus-maze and allowed to explore for 5 min. During this period, 12 behavioral categories (number of entries and time spent in the open and enclosed arms, total arms entries, attempts to enter open and closed arms, closed-arm returns, latency of first closed-arm entry, total immobility time, total grooming time, total rearings, total head-dippings, and total stretch attend posture) were recorded. The results showed that anxiety increased with age and that protein malnutrition produced alterations in the ontogeny of exploratory behaviors. It was shown that malnourished rats maintained or increased exploration in the maze with age, in contrast to well-nourished animals, which exhibited a steady decrease in exploration as they matured. The higher number of entries and time spent in the open arms suggest that the protein malnutrition causes a permanent increase in the impulsiveness and/or an increased drive to explore open-arm novelty, leading to a behavior consistent with lower anxiety in malnourished animals, relative to that in well-nourished animals, in this naturalistic animal model of anxiety.

Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol

Buspirone is renowned for its highly inconsistent effects in animal models of anxiety. In the present study, the effects of acute (0.63-5.0 mg/kg) and chronic (1.25-5.0 mg/kg, daily, 15 days) buspirone treatment on the behaviour of mice in the elevated plus-maze test were assessed using a recently developed ethological scoring method. On acute administration, a selective reduction in risk assessment behaviours was observed at 1.25 mg/kg; these mild anxiolytic-like effects were maintained at higher doses (2.5-5.0 mg/kg) which also reduced measures of general activity. Similar, though more potent, effects were observed with chronic administration; the lowest dose tested (1.25 mg/kg) reduced open arm entries and total stretch attend postures while higher doses profoundly reduced all major indices of anxiety (traditional and novel) and, concomitantly, suppressed total entries and rearing. Acute administration of haloperidol (0.0125-0.1 mg/kg) appeared to mimic the behavioural suppressant effects of buspirone without selectively affecting anxiety-related measures at any dose. It is suggested that the anti-anxiety and behavioural suppressant profile of buspirone may reflect combined action at 5-HT1A and D2 receptors, respectively. Results are discussed in relation to the utility of risk assessment as a sensitive index of anxiety in models based upon unconditioned behaviour.