Increase In Horizontal Activity Research Articles

Locomotion changes in methamphetamine and amphetamine withdrawal: a systematic review.

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals' locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.

Combined effects of mephedrone and cocaine on locomotor activity and conditioned place preference in male Sprague-Dawley rats.

Mephedrone (MEPH) is one of several synthetic cathinone derivatives and a common constituent of illicit 'bath salts'. Concomitant use of MEPH with other psychostimulants is common among recreational users, but their combined effects have not been evaluated rigorously. In experiment 1, 56 male Sprague-Dawley rats were administered saline, MEPH (1 or 5 mg/kg), COC (5 mg/kg), or a mixture of MEPH (1 or 5 mg/kg) + COC (5 mg/kg) for seven consecutive days. Following a 10-day drug washout, rats were given a challenge injection of COC (5 mg/kg). Locomotor activity was recorded for 60 minutes immediately before and for 60 minutes immediately after injections on days 1, 7, and 17. In experiment 2, an unbiased conditioned place preference procedure was implemented over a 10-day period with a separate group of 66 male Sprague-Dawley rats randomly assigned to similar drug treatments used in experiment. Results of experiment 1 indicated significant increases in horizontal activity after repeated treatment with MEPH+COC mixtures, but not with either drug alone. Additionally, rats pretreated with MEPH + COC mixtures exhibited an augmented response to cocaine following drug abstinence. Evidence for CPP was established in rats treated with 5 mg/kg MEPH, 5 mg/kg COC and the 5 mg/kg MEPH + 5 mg/kg COC mixture. In conclusion, cocaine and mephedrone may have additive locomotor stimulant effects, although further assessment with a wider range of dose combinations must be evaluated. As a precautionary note, concurrent use of these substances may pose an enhanced risk for abuse.

Repeated exposure to 3,4-methylenedioxypyrovalerone and cocaine produces locomotor sensitization with minimal effects on brain monoamines

Synthetic cathinones, known as “bath salts” on the illicit drug market, pose a significant public health concern. 3,4-Methylenedioxypyrovalerone (MDPV), one of several popular constituents of illicit bath salts, produces similar pharmacological actions to cocaine, albeit with greater potency and efficacy. The present study sought to characterize behavioral and neurochemical effects of repeated exposure to MDPV alone and in combination with cocaine. Male Sprague-Dawley rats were randomly assigned to one the following four treatments, administered once daily for seven days: 1 mg/kg MDPV, 5 mg/kg cocaine, 1 mg/kg MDPV +5 mg/kg cocaine, or saline. Locomotor activity was assessed for 1 h immediately before and 1 h immediately after injections on days 1 and 6. Brains were harvested 20 min after the final injection on day 7 and brain tissue punches were obtained to determine monoamine content within the anterior striatum, medial prefrontal cortex, and nucleus accumbens using High-Performance Liquid Chromatography (HPLC). Drug-induced increases in horizontal activity were significantly greater on treatment day 6 compared to treatment day 1 in all three drug treatment groups in comparison to the saline control group. MDPV produced significantly higher increases in activity compared to either saline or cocaine, although concurrent treatment with MDPV and cocaine produced sub-additive effects. Neurochemical analyses provided no evidence of alterations in total monoamine content following repeated administration of MDPV, cocaine, or the MDPV + COC mixture. Further investigations targeting possible changes in DA receptor sensitivity following repeated exposure to MDPV may help elucidate the mechanistic changes responsible for MDPV-induced behavioral sensitization.This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’

Sensitization to the locomotor stimulant effects of “bath salt” constituents, 4‐methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats

BackgroundSynthetic cathinones, 4-methylmethcathinone (4-MMC) and 3,4‐methylenedioxypyrovalerone (MDPV), serve as a substrate or blocker at monoaminergic transporters, respectively, and produce locomotor stimulant effects in rodents. The present study investigated in rats the effects of repeated exposure to 4‐MMC, MDPV, or mixtures of the two on the induction of locomotor sensitization and expression of cross-sensitization to cocaine. MethodsSeventy-two male Sprague-Dawley rats received daily intraperitoneal injections of saline, MDPV (0.5mg/kg), 4-MMC (0.5, 1.0, or 2.0mg/kg) or mixtures of 0.5mg/kg MDPV+4‐MMC (0.5, 1.0, or 2.0mg/kg) for seven consecutive days. Locomotor activity was recorded on days 1 and 7 and again after an acute injection of 5mg/kg cocaine following a 10day drug washout period. ResultsRats injected with 0.5mg/kg MDPV, 0.5, 1.0, or 2.0mg/kg 4-MMC, or 2.0mg/kg 4-MMC+0.5mg/kg MDPV displayed time-dependent increases in horizontal activity that were augmented on day 7 compared to day 1. In addition, rats pretreated with 0.5mg/kg MDPV, 2.0mg/kg 4-MMC, or mixtures of 4-MMC+MDPV displayed an enhanced response to cocaine. ConclusionsLocomotor responses sensitize to MDPV and to certain mixtures of MDPV and 4-MMC following repeated dosing. Furthermore, previous exposure to these substances may produce cross-sensitization to the locomotor stimulant effects of cocaine. Considered together with recent findings that 4-MMC and MDPV have different sites of action, but both influence monoaminergic functioning, further investigations utilizing a variety of behavioral assays may prove informative regarding the abuse liability of synthetic cathinone mixtures.

Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats

Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145–175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is needed on aging-related susceptibility to environmental contaminants.

Modeling Parkinson's disease genetics: Altered function of the dopamine system in Adh4 knockout mice

Class IV alcohol dehydrogenase (ADH4) efficiently reduces aldehydes produced during lipid peroxidation, and may thus serve to protect from toxic effects of aldehydes e.g. on neurons. We hypothesized that ADH4 dysfunction may increase risk for Parkinson's disease (PD) and previously reported association of an ADH4 allele with PD. We found that a promoter polymorphism in this allele induced a 25–30% reduction of transcriptional activity. Based on these findings, we have now investigated whether Adh4 homo- (Adh4−/−) or heterozygous (Adh4+/−) knockout mice display any dopamine system-related changes in behavior, biochemical parameters or olfaction compared to wild-type mice. The spontaneous locomotor activity was found to be similar in the three groups, whereas administration of d-amphetamine or apomorphine induced a significant increase in horizontal activity in the Adh4−/− mice compared to wild-type mice. We measured levels of monoamines and their metabolites in striatum, frontal cortex and substantia nigra and found increased levels of dopamine and DOPAC in substantia nigra of Adh4−/− mice. Investigation of olfactory function revealed a reduced sense of smell in Adh4−/− mice accompanied by alterations in dopamine metabolite levels in the olfactory bulb. Taken together, our results suggest that lack of Adh4 gene activity induces changes in the function of the dopamine system, findings which are compatible with a role of loss-of-function mutations in ADH4 as possible risk factors for PD.

Prenatal Nicotine and/or Cocaine Differentially Alters Nicotine‐Induced Sensitization in Aging Offspring

Repeated exposure to psychostimulant drugs can result in behavioral sensitization, an amplified response in locomotor activity and stereotypy, which is used to model aspects of drug addiction. The expression of behavioral sensitization, induced by i.p. injections of nicotine once daily for 5 days, was examined in 450-day-old male rats exposed prenatally on GD 8-20 to one of the following conditions: (1) low nicotine: 2.5 mg/kg/day nicotine [LN]; (2) high nicotine: 5.0 mg/kg/day nicotine [HN]; (3) low nicotine/high cocaine: 2.5 mg/kg/day nicotine plus 40 mg/kg/day cocaine [LN/HC]; (4) high nicotine/low cocaine: 5.0 mg/kg/day nicotine plus 20 mg/kg/day cocaine [HN/LC]; (5) pair-fed controls: food intake yoked to HC dams [PF]; and (6) saline controls: daily injections of 0.9% NaCl solution[SAL]. Initial injection of nicotine did not alter activity or stereotypy in comparison to saline injections, with offspring in all prenatal treatment groups showing a desensitization to nicotine. Five consecutive daily nicotine injections resulted in behavioral sensitization in HN and HN/LC prenatal drug groups. Offspring exhibited an increase in horizontal activity that was evident on day 3, and still present after a 1.0 mg/kg i.p. nicotine challenge 72 hours after the last injection (day 8). SAL offspring exhibited attenuated sensitization. In contrast, nicotine sensitization was not seen in the LN, HC/LN, and the PF offspring; activity remained at the level seen after the initial injection of nicotine. Moreover, nicotine significantly reduced total activity in the LN and PF groups in comparison with their saline-injected counterparts. These data suggest that gestational exposure to high-dose nicotine, either alone or in combination with cocaine, may carry a greater risk than low-dose nicotine exposure of stimulant abuse in later life.

Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation

Altered cholinergic function is considered as a potential contributing factor in the pathogenesis of schizophrenia. We hypothesize that cortical cholinergic denervation may result in changes in glutamatergic activity. Therefore, we lesioned the cholinergic corticopetal projections by local infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of rats. Possible effects of this lesion on glutamatergic systems were examined by phencyclidine-induced locomotor activity, and also by N-methyl-D-aspartate receptor binding. We find that cholinergic lesioning of neocortex leads to enhanced sensitivity to phencyclidine in the form of a dramatic increase in horizontal activity. Further, N-methyl-D-aspartate receptor binding is unaffected in denervated rats. These results suggest that aberrations in cholinergic function might lead to glutamatergic dysfunctions, which might be of relevance for the pathophysiology for schizophrenia.

Sumanirole, a Highly Dopamine D2-Selective Receptor Agonist: In Vitro and in Vivo Pharmacological Characterization and Efficacy in Animal Models of Parkinson's Disease

The purpose of this study is to demonstrate that sumanirole is a novel dopamine receptor agonist with high in vitro and in vivo selectivity for the D(2) receptor subtype. Sumanirole, (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Z)-2-butenedioate (1:1), is unique; it has greater than 200-fold selectivity for the D(2) receptor subtype versus the other dopamine receptor subtypes in radioligand binding assays. In cell-based assays, sumanirole is a fully efficacious agonist, with EC(50) values between 17 and 75 nM. In animals, sumanirole elicits many physiological responses attributed to D(2)-like receptor function. In rats, sumanirole is a full agonist for elevation of striatal acetylcholine levels (ED(50) = 12.1 micromol/kg i.p.). Sumanirole s.c. dose dependently decreased plasma prolactin levels and depressed dopamine neuron firing rates in the substantia nigra pars compacta with an ED(50) of 2.3 micromol/kg i.v. This high selectivity for D(2) receptors translates into excellent locomotor stimulant activity in animal models of Parkinson's disease. In reserpinized, alpha-methyl-para-tyrosine-treated rats, sumanirole caused a significant and sustained increase in horizontal activity at doses > or =12.5 micromol/kg s.c. In unilateral 6-hydroxydopamine-lesioned rats, sumanirole caused profound, sustained rotational behavior and was substantially more efficacious than any other agonist tested. Sumanirole-stimulated rotational behavior was blocked by the dopamine receptor antagonist haloperidol. Sumanirole dose dependently improved disability scores and locomotor activities of two of three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In summary, sumanirole is the first published selective D(2) receptor agonist. The compound has activity in animal models of dopamine hypofunction and has a high level of efficacy in animal models of Parkinson's disease.

Gender differences in modulatory effects of tamoxifen upon the nigrostriatal dopaminergic system

It has been demonstrated that the gonadal steroid hormone estrogen can exert neuroprotective effects upon the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA)-induced neurotoxicity in female, but not male, mice. In contrast, the anti-estrogen, tamoxifen (TMX) can function as a NSDA neuroprotectant within both female and male mice. In an attempt to understand these effects of TMX, the effects of this anti-estrogen upon both behavioral and neurochemical indices of NSDA function were examined within female and male mice following treatment with MA. In general, TMX exerted markedly different (bi-directional) effects upon NSDA function between female and male mice. Notably, treatment with TMX resulted in a relative decrease in striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations within male mice and a relative increase in female mice when treated with MA to produce a significant gender difference. Similar effects were obtained for locomotor behaviors related with NSDA function. That is, TMX produced increases in horizontal activity, number of movements and total distance traveled within MA-treated female mice resulting in statistically significant gender differences for the two former parameters. For non-locomotor behaviors, like time occupying the center and margin of the cage, TMX-treated male mice showed statistically significant increases and decreases compared within TMX-treated female mice, respectively. These results show that in contrast to the similar neuroprotective effects of TMX upon MA-induced NSDA neurotoxicity, a number of other NSDA indices induced by MA show markedly different response profiles between TMX-treated female and male mice.

Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson's disease.

The present study was designed to determine the potential of CB1 cannabinoid receptor modulating compounds in the treatment of L-3,4-dihydroxyphenylalanine (L-dopa)-induced dyskinesia in Parkinson's disease. In the reserpine-treated rat model of parkinsonism, administration of a high dose of L-dopa (150 mg/kg) but not of Cl-APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1-3 mg/kg) reduced the increase in vertical activity elicited by L-dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212-2 (0.1-3 mg/kg) reduced the L-dopa-induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by L-dopa. WIN55,212-2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl-APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine-treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl-APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine-treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1-1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L-dopa (150 mg/kg) in the reserpine-treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of L-dopa and may be useful for the treatment of the dyskinesia associated with long-term L-dopa treatment of Parkinson's disease.

Enhanced locomotor stimulation by NMDA receptor antagonists in alcohol-sensitive ANT rats

The ability of the antagonists for the N-methyl- d-aspartate (NMDA) type of glutamate receptor to modulate locomotor activity were compared in alcohol-sensitive (or alcohol-nontolerant, ANT) and alcohol-insensitive (or alcohol-tolerant, AT) rat lines. Both rat lines showed altered locomotor activity after acute injections of a competitive antagonist (LY235959), a glycine-site antagonist (L-701,324), or noncompetitive antagonists [MK-801, phencyclidine (PCP), and ketamine] of the NMDA receptor. MK-801 at 0.5 mg/kg caused a strong increase in horizontal activity in both rat lines, the effect being significantly greater in the ANT rats. There was a subpopulation among AT rats that was almost completely unresponsive to MK-801. This insensitivity to MK-801 correlated with the lack of c- fos induction in the retrosplenial and cingulate cortices. Fos immunoreactive cells in these brain regions after MK-801 treatment were more numerous in ANT than AT rats, although c- fos induction in the inferior olivary nucleus was similar in all animals after MK-801. The ANT rats showed greater locomotor stimulation also after ketamine and LY235959, while stimulation induced by PCP and depression induced by L-701,324 did not differ between the rat lines. The data suggest that altered NMDA receptor-mediated processes may correlate with differences in innate alcohol sensitivity in the ANT/AT rat model.

Release of Dopamine in the Nucleus Accumbens Caused By Stimulation of the Subiculum in Freely Moving Rats

Stimulation of the ventral subiculum of the hippocampus activates the hippocampal-accumbens pathway and increases locomotor activity. Dopaminergic terminals in the nucleus accumbens have also been implicated in initiation of locomotor activity, and the release of dopamine in the nucleus accumbens is critical for locomotor responses initiated from the subiculum to occur. We have demonstrated release of dopamine in the nucleus accumbens using in vivo microdialysis after stimulation of the ventral subiculum with NMDA. Extracellular dopamine level in the nucleus accumbens was significantly increased by 40% over baseline as a result of NMDA stimulation of the ventral subiculum. This stimulation also caused more than a 40-fold increase in horizontal activity and total distance covered by the rats. Injection of saline into the subiculum caused neither a change in the dopamine level nor an increase in animal's activity. The dynamics of the measured changes in dopamine overflow correlated with the time course of locomotor changes. The results demonstrate that stimulation of the ventral subiculum causes release of dopamine in the nucleus accumbens which parallels the increase in locomotor activity.

Effects of MK-801 on rough-and-tumble play in juvenile rats

Effects of the noncompetitive N-methyl- d-aspartate (NMDA) channel blocker, MK-801, on play behavior and activity were assessed in juvenile rats. A low dose (0.025 mg/kg) of MK-801 significantly increased both pinning and dorsal contacts, two indices of play behavior in the rat. Higher doses (≥0.1 mg/kg) significantly reduced both measures of play, with play being virtually abolished at 0.2 mg/kg. Simultaneous measurements of activity indicated that the reductions of play at the higher doses were accompanied by significant increases in horizontal activity. There was also a dose-related reduction in rearing, which was significant at all doses. When juvenile rats were tested individually for activity in an open field, MK-801 increased horizontal activity at 0.2 mg/kg and decreased rearing at all doses. So while the effects of MK-801 on play are biphasic, the effects of this compound on locomotor activity, per se, are linear. These data suggest that the effects of NMDA channel blockade on overall activity and play are mediated through independent neural systems.

Sensitization to cocaine's motor activating properties produced by electrical kindling of the medial prefrontal cortex but not of the hippocampus

A substantial body of evidence has accumulated that implicates NMDA systems in the neural changes that are associated with the development of both electrical kindling of limbic sites and sensitization to the behavioral effects of repeated stimulant exposure. This study sought to establish whether electrical kindling of the brain was a sufficient condition for inducing sensitization to cocaine's motor activating effects and, if so, whether the cross sensitization was a result of kindling of a specific locus. Rats received daily electrical stimulation of either the medial prefrontal cortex or the hippocampus. Other rats received the electrode implants and were handled daily but received no electrical stimulation. Stage 5 seizures developed in response to the stimulation in 32–35 days. Once this criterion of kindling was established and following a 14 day waiting period the effectiveness of cocaine (0.0, 5.0 or 10.0 mg/kg) in elevating horizontal motor activity was determined. For all 3 groups (sham controls, prefrontal cortical and hippocampal stimulated rats) cocaine produced a dose-dependent increase in horizontal activity. The slam controls and hippocampal rats did not differ in the magnitude of the cocaine-produced effect. However, rats that had received stimulation of the prefrontal cortex showed heightened levels of cocaine-induced activity that were particularly apparent in response to 10.0 mg/kg cocaine. These data suggest that kindling of the prefrontal cortex had sensitized rats to the behavioral effects of cocaine. Since the NMDA system has been implicated in both electrical kindling and sensitization produced by repeated stimulant exposures it is possible that the development of behavioral sensitization is a result of increased sensitivity of specific glutamatergic inputs that arise from a prefrontal cortical substrate and project to cocaine-sensitive sites.

Effects of several amnesic drugs on the habituation of exploratory activity in mice as indexed by horizontal and vertical activities

1. 1. The effects of several drugs on the habituation of exploratory activity in mice were investigated by using animal movement analyzing systems which could detect horizontal and vertical activities. 2. 2. Habituation was regarded as the difference between exploratory activity measured first (session 1) and that measured second (session 2). 3. 3. Scopolamine (1, 3 and/or 6 mg/kg), pirenzepine (20 and 40 μg) injected immediately after session 1, cycloheximide (30 mg/kg), diazepam (1, 2 and/or 4 mg/kg) and dizocilpine (0.05, 0.1 and/or 0.2 mg/kg), unlike butylscopolamine (1, 3 and 6 mg/kg) or haloperidol (0.2 and 0.4 mg/kg), significantly increased horizontal activity but not always vertical activity in session 2. 4. 4. From the results obtained, it appears that the increase in horizontal activity in session 2 is more appropriate as an indicator of the impairments of memory processes than that in vertical activity.

Chromogranin A applied to the nucleus accumbens decreases locomotor activity induced by activation of the mesolimbic dopaminergic system in the rat

The aim of the study was to obtain supporting evidence, using a behavioral paradigm, of the hypothesis that chromogranin A attenuates transmitter release in the CNS. We studied the effects of chromogranin A injected into the nucleus accumbens on locomotor activity triggered by application of picrotoxin into the ventral tegmental area of rats. Injection of picrotoxin into the ventral tegmental area, which is known to disinhibit dopaminergic mesolimbic neurons, caused a significant increase in horizontal activity. Distance covered during locomotion and movement time increased more than twofold, whereas stereotypy time and number, indices of nonlocomotor behavior, were not significantly affected by picrotoxin. Pressure injection of Chromogranin A into the nucleus accumbens prior to injection of picrotoxin into the ventral tegmental area prevented these locomotor effects and had little or no effect on nonlocomotor behavior. Similarly, the picrotoxin-induced activity was prevented by injecting cobalt chloride into the nucleus accumbens. The results show that chromogranin A has an attenuating effect, either directly or indirectly, on dopaminergic neurotransmission in the nucleus accumbens that can be exemplified by inhibiting picrotoxin-induced locomotor activity. Further studies are needed to determine the mechanism of chromogranin A action in the nucleus accumbens.

MU and delta opioid receptors control differently the horizontal and vertical components of locomotor activity in mice

The present study investigated the role of mu and delta opioid receptors in the control of the horizontal and vertical components of locomotion. Mice received intracerebroventricularly (i.c.v.) enkephalin analogs specific for either the mu or delta opioid receptors. The administration of the specific mu agonist [D-Ala 2-NMePhe 4-Gly 5(ol)] enkephalin (DAGO) induced a dose-dependent increase in horizontal activity and a decrease in vertical activity. The specific delta agonist [D-Pen 2, D-Pen 5] enkephalin (DPDPE) increased both components of motor activity. The opiate antagonist naltrexone reversed the effects of DAGO, but did not influence the effects of DPDPE on motor activity. The pretreatment with the delta opiate antagonist ICl 154, 129 completely reversed the effects of DPDPE on locomotion but antagonized only partially the effects of DAGO on locomotion. These results indicate that the two components of locomotor activity — horizontal and vertical activity — are modulated differently by the stimulation of mu or delta opioid receptors.