p-Chloroamphetamine: Effects on tonic immobility, activity, and temperature in chickens.

The effects of parachloroamphetamine (PCA) on tonic immobility (TI) duration, activity, and temperature in 216 Production Red chickens were examined in 6 experiments. 10 or 15 mg/kg PCA ip produced a significant attenuation of TI duration. Involvement of norepinephrine or dopamine in this effect was considered questionable, since catecholamine synthesis inhibition with alpha-methylparatyrosine did not alter PCA attenuation of TI duration. However, serotonin synthesis inhibition with parachlorophenylalanine produced a blockade of the PCA effect on TI when Ss were tested 60 min after PCA. A competing response interpretation of the PCA effect in terms of enhanced motor activity was ruled out, since, in contrast to the hyperactivity observed in mammals, PCA produced a decrease in both open-field and stabilimeter activity. A PCA-induced decreased in core temperature was observed in Exp VI. Together with previous findings, results suggest a mammalian–avian reversal in drug effects. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of castration and testosterone in experimental models of depression in mice.

In the behavioral despair (forced swimming) test and in the tail-suspension test, long-term (30–32 days) castration significantly increased the duration of immobility in mice. Testosterone propionate (1 or 10 mg/kg/day–2 sc for 4 days), although not affecting the duration of immobility in sham-operated mice, reduced the duration of immobility in castrated mice to within normal limits. Desipramine (20 mg/kg ip) decreased the duration of immobility both in sham-operated and in castrated animals. These results indicate that castration favors an inactive behavior and that testosterone, although having no "antidepressant" effect per se, is necessary for the male animal to cope normally with adverse environmental situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic modulation of tonic immobility in the rabbit (Oryctolagus cuniculus).

Conducted a study with 13 adult Dutch Belt rabbits to determine the effects of the anticholinergic agent scopolamine and the cholinergic agent physostigmine on tonic immobility in rabbits. Recordings of the EEG activity from cortex and hippocampus were also made before, during, and after each test session. Scopolamine significantly prolonged the response and produced large amplitude slow wave activity in the EEG of both cortex and hippocampus. Physostigmine significantly shortened the duration of immobility and increased rhythmic slow activity in the frequency range of 5.5-9.1 Hz in the hippocampus while producing a desynchronized cortical rhythm. It is suggested that the cortex and hippocampus play a role in modulating tonic immobility duration by inhibiting the brain-stem structures thought to control this response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of dopaminergic and cholinergic neurotransmission by tachykinin NK3 receptor stimulation: an in vivo microdialysis approach in guinea pig

The regulation of dopaminergic and cholinergic function by neurokinin-3 (NK3) receptor activation was examined in vivo in urethane-anaesthetized guinea pigs with microdialysis probes. The local application of the NK3 tachykinin receptor agonist senktide in the region of dopamine cell bodies (pars compacta of the substantia nigra and ventral tegmental area) and in the area of cholinergic cell bodies (septal area) markedly enhanced the extracellular dopamine (DA) and acetylcholine (ACh) concentration throughout their respective target areas, i.e. striatum, nucleus accumbens, prefrontal cortex for dopaminergic systems and hippocampus for cholinergic neurons. The enhancing effect of senktide on neurotransmitter release was dose dependently blocked by the selective non-peptide NK3 receptor antagonist SR142801 (0.1-1 mg/kg, i.p.), whereas its inactive S-enantiomer SR142806 (0.3-1 mg/kg, i.p.) did not exert any antagonistic activity on the effect of intranigral or intraseptal application of senktide. These results demonstrate that NK3 receptors can modulate the activity of central DA and ACh systems.     

Effect of serotonergic and catecholaminergic antagonists on mild-stress-induced excessive grooming in the rat.

Studied the action of the dopamine antagonist haloperidol, the serotonin antagonists methysergide and pizotifen (pizotyline), and the alpha- and beta-adrenoceptor antagonists phentolamine and levo-propranolol on the grooming response to a mild stress in male Holtzman rats. Excessive grooming induced by 2 ip injections of physiological saline did not modify open-field locomotion in 5-min trials. Methysergide (15 mg/kg, ip) and pizotyline (5 mg/kg, ip) selectively prevented the grooming response to saline without affecting locomotion. Haloperidol (.4 mg/kg) also prevented excessive grooming. However, it also impaired locomotion. Phentolamine (20 mg/kg) and levo-propranolol (20 mg/kg) did not prevent the excessive grooming in response to saline and did not affect locomotion. Results suggest that some serotonergic pathways in the brain are involved in the grooming response to a mild stress and support previous findings on the role of dopaminergic systems on this activity. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine-induced effects on isolation stress in neonatal rats.

The effects of cocaine administration on isolation-induced vocalizations and activity levels in 10-day-old rat pups were examined. Day 10 pups given cocaine (1.25, 2.5, 5, 10, and 20 mg/kg ip) vocalized significantly less than their caffeine- (10 mg/kg) and saline-administered siblings during a 5-min isolation period. Cocaine- and caffeine-administered pups also demonstrated a significant increase in overall activity compared with controls. In addition, ip administration of the dopamine antagonist haloperidol (0.5 and 1.0 mg/kg) before 1.25 and 2.5 mg/kg cocaine produced a significant elevation in vocalizations compared with saline pretreatment, which indicates a blocking of cocaine's effect on calling behavior. These results suggest that the endogenous dopamine system involved with reinforcement and reward may quell the stress of isolation in the infant rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selegiline prevents long-term changes in dopamine efflux and stress immobility during the second and third weeks of abstinence following opiate withdrawal

Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline on in vitro measures of dopamine efflux following opiate withdrawal. Treatment with 2.0 mg/kg/day of selegiline did not modify the severity of opiate withdrawal, as assessed by weight loss over the first 3 days of abstinence. Opiate withdrawal increased immobility in response to a forced warm water swim test performed during the second and third weeks of abstinence following the onset of withdrawal. Brain slices obtained from the nucleus accumbens of opiate-withdrawn animals immediately following swim stress testing displayed diminished efflux of tritiated dopamine after two in vitro exposures to cocaine or amphetamine. Cocaine increases neurotransmitter efflux through blockade of dopamine reuptake, while amphetamine augments efflux by stimulating release of dopamine from intracellular storage vesicles. Although slices from opiate withdrawal subjects showed decreases in efflux after in vitro treatment with these agents, no differences were observed after exposure to 4-aminopyridine, which increases neurotransmitter release by prolonging action potential duration. These findings indicate mechanisms of action that are specific for catecholamine neurotransmitter systems are important for demonstrating long-term changes in dopaminergic function following opiate withdrawal. Selegiline prevented decreases in the efflux of tritiated dopamine in slices obtained from opiate-withdrawn subjects. In addition, selegiline decreased withdrawal-induced immobility during warm water swim testing. In conclusion, treatment with selegiline can prevent long-term changes in stress-induced immobility and deficits in presynaptic dopaminergic function that occur following the opiate withdrawal syndrome.     

Spontaneous and drug-stimulated locomotor activity after the administration of pertussis toxin into the ventral tegmental area

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) produces an enhanced locomotor response to amphetamine. In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergic agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomotor activity with a latency of 4 d. This activity was markedly increased by day 6 and remained elevated for at least 28 d after PTX treatment. This increased spontaneous locomotor activity of PTX-treated animals was antagonized by the administration of the D1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D2 receptor antagonist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomotor cages, the animals showed a markedly enhanced motor response to amphetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc). The heightened locomotor responses to these dopaminergic agonists could be elicited for at least 2 mo after PTX administration. The enhanced response to amphetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), but not by eticlopride (0.1 mg/kg). The increased response to apomorphine in PTX-treated animals was inhibited by SCH23390 (0.1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc). Both of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an increase in spontaneous and drug-induced locomotor activity in which D1 receptors seem to play an important role.     

Abnormalities of the left ventricular outflow tract associated with discrete subaortic stenosis in children: an echocardiographic study

Although the antiaggressive properties of several atypical neuroleptics are known, the actions of tiapride (a selective dopaminergic D2-receptor antagonist) on agonistic behavior have not been explored and there are no studies comparing acute and subchronic effects of this compound on aggression in rodents. In this work, the effects of tiapride (20-100 mg/kg, IP), administered acutely or subchronically for 10 days, on agonistic behaviour elicited by isolation in male mice were examined. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Tiapride decreased time spent in offenssive behaviors significantly, without an impairment of motor activity (60 and 80 mg/kg). Moreover, no tolerance to tiapride antiaggressive activity was observed after repeated administration of the drug. On the contrary, the action on immobility showed a clear tolerance development with repeated injections (100 mg/kg). The divergence found in the temporal course of tolerance to tiapride in its antiaggressive and motor effects is discussed.     

Motor effects of lamotrigine in naive and dopamine-depleted mice

Lamotrigine (3,5-diamino-6-[2,3-dichlorphenyl]-1,2,4-triazine) has been hypothesised to possess antiparkinsonian activity, by inhibiting the release of glutamate from basal ganglia neurones. This study therefore examined the motor effects of lamotrigine in naive and reserpine-treated mice and its interactions with dopaminergic agonists. In normal mice, lamotrigine (5-80 mg/kg i.p.) decreased spontaneous locomotor activity with high doses (> or = 40 mg/kg) causing moderately severe impairment to posture and gait. In mice treated 24 h beforehand with reserpine (5 mg/kg i.p.), lamotrigine (5-40 mg/kg i.p.) had no effect on akinesia by itself and did not alter the locomotion induced with the selective dopamine D1 receptor agonist 2,3,4, 5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.). By contrast, motor responses to the dopamine D2 receptor-selective agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and to the dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in the presence of benserazide, 100 mg/kg i.p.), were significantly potentiated by 10 and 40 mg/kg i.p. lamotrigine respectively. It is suggested that lamotrigine may enhance the antiakinetic action of L-DOPA in parkinson-like mice by increasing motor responding mediated by dopamine D2 but not dopamine D1 receptors. This interaction profile of lamotrigine with dopamine D1 and D2 receptor mechanisms is opposite to what one sees with antagonists of glutamate receptors.     

Buspirone enhances immobility in the forced swim test in mice

We studied the effects of buspirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on duration of immobility in mice in the forced swim test. Buspirone [3-10 mg/kg, intraperitoneally (IP)] potently and dose dependently increased the duration of immobility in mice. In contrast, following a single dose of 8-OH-DPAT (1-3 mg/kg, IP), there was a dose-dependent decrease in the duration of immobility. Pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (200 mg/kg, IP, 3 days before further drug treatment) did not alter the effects of buspirone or 8-OH-DPAT. The increase in the duration of immobility induced by buspirone (3 mg/kg, IP) was blocked by NAN-190 [1-(2-methoxyphenyl)-4-(4-[2-phthalimido]butyl)-piperazine hydrobromide, 1 mg/kg, IP], a postsynaptic 5-HT1A receptor antagonist. However, the effect of 8-OH-DPAT (1 mg/kg, IP) was not blocked by NAN-190 (1 mg/kg, IP). The effect of buspirone (3 mg/kg, IP) was blocked by apomorphine (0.3 mg/kg, IP), a dopamine receptor agonist. Based on the results of this study, it is suggested that the effects of buspirone and of 8-OH-DPAT on immobility in the forced swim test may occur through different mechanisms.     

Morphine catalepsy as an adaptive reflex state in rats.

A series of experiments with 56 male Long-Evans rats demonstrated that catalepsy induced by morphine sulfate (20–80 mg/kg, ip) consists of 2 complementary, but opposite, behavioral extremes (rigid immobility and sudden locomotor bursts), each of which could be controlled by distinct classes of external stimuli. When stimuli that involved pain and/or nonnociceptive skin pressure were tonic (continuous), morphine-induced EEG deactivation and behavioral immobility were potentiated, even to the extent that a stimulation-bound reversible coma resulted. In contrast, phasic (discrete stimulation produced behavioral and/or EEG activation. EEG and behavioral rebound effects were observed following stressful (intense, prolonged) stimuli. On the basis of the observed stimulus controls, sensorimotor characteristics, and EEG reactions, it is suggested that similarities may exist between morphine-induced catalepsy and defensive reactions of immobility and escape in drug-free animals (i.e., the adaptive death-feigning reflex). (59 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of concurrently administered copper and mercury on phagocytic cell activity and antibody levels in guinea pigs with experimental ascariasis

The dopamine (DA) D2/D3 antagonist (-)eticlopride (0.02, 0.05 and 0.1 mg/kg), dose-dependently increased immobility in the mouse tail-suspension test. Chronic treatment with the same compound (0.05, 0.1 mg/kg, x 14 days) produced a different effect, decreasing immobility when animals were tested 24 h after the last injection. The DA D3 agonist, 7-OH-DPAT, acutely administered before the same test, behaved biphasically, increasing and decreasing mice immobility at low (0.05 and 0.1 mg/kg) and high (1 and 2 mg/kg) doses, respectively. Chronically administered 7-OH-DPAT reduced the immobility time at 2 mg/kg but not at 0.1 mg/kg. These effects, coupled with measurements of locomotor activity and evaluation of mice behaviour in different conditions, are discussed in the light of putative DA involvement in depressive states and are considered as predicting antidepressant potential.     

A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides

The effects of L-type voltage-dependent Ca2+ channel blockers on apomorphine, bromocriptine and morphine-induced changes in locomotor activity were examined in mice. Apomorphine (4 mg/kg) and morphine (20 mg/kg) produced locomotor stimulation. Bromocriptine (8 mg/kg) produced a biphasic effect on motor behaviour, an early depressant phase, followed by locomotor stimulation. Amlodipine (2.5 mg/kg), nicardipine (10 mg/kg), diltiazem (10 mg/kg) and verapamil (10 mg/kg), which by itself did not affect locomotor activity, inhibited the stimulant phase of bromocriptine without altering the depressant phase, while they did not affect apomorphine- and morphine-induced locomotor stimulation. Apomorphine, bromocriptine and morphine-induced locomotor stimulation was decreased by SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol) (0.05 mg/kg) or haloperidol (0.1 mg/kg). These results indicate that L-type voltage-dependent Ca2+ channels are involved in the motor stimulant effect of bromocriptine, but not in apomorphine- and morphine-induced locomotor stimulation. The effects of Ca2+ channel blockers on the dopaminergic system appears not to be directly related to dopamine receptor blockade.     

Dopaminergic parameters during social isolation in low- and high-active mice

Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to locomotor activity, [3H]-spiperone binding in the striatum, striatal, and cortical dopamine metabolism, and presynaptic dopaminergic sensitivity to apomorphine (0.75 mg/kg; i.p.). Isolated HAM and LAM showed increased locomotor activity compared to group-housed mice after long-term isolation (6-18 weeks). Considering the studied dopaminergic parameters, it has been found that social isolation did not affect striatal D2 receptors, striatal and cortical dopamine metabolism, and apomorphine-mediated reduction of dopaminergic metabolism. The change of housing conditions was generally associated with an increase of cortical dopamine metabolism after 1 week. Activity type specific differences in group-housed LAM and HAM were found in the basal striatal dopamine metabolism and in the sensitivity of the nigrostriatal system to autoreceptor activation. The reduced striatal dopamine metabolism and the higher presynaptic sensitivity of HAM may be related to their high active running wheel behavior.     

Role of rpoS in the regulation of glutathione oxidoreductase (gor) in Escherichia coli

Caffeine (10-40 mg/kg, p.o.) enhanced locomotor activity (LA). Administration of GABA antagonist, bicuculline (0.5-1.0 mg/kg, i.p.), potentiated this caffeine-induced increase of LA, as well as LA of control rats. Treatment with the GABA agonist, muscimol (0.25-1 mg/kg, i.p.) or dopaminergic antagonist, haloperidol (0.25-1 mg/kg, i.p.) or muscarinic receptor blocker, atropine (3.75-5 mg/kg, i.p.), or inhibitor of acetylcholine esterase physostigmine (0.05-0.30 mg/kg, i.p.) or nicotine (0.5-1.5 mg/kg, i.p.) an nicotinic receptor agonist all decreased the LA of both caffeine-treated and control rats. Haloperidol-induced reduction in caffeine-induced increase in LA was found to be withdrawn with higher dose of caffeine. The dopamine agonist L-Dopa (75-150 mg/kg, p.o.) along with carbidopa (10 mg/kg, p.o.) increased the LA in control rats and potentiated the LA of caffeine treated rats. The haloperidol attenuated the bicuculline-induced increase in LA and atropine or physostigmine attenuated the bicuculline or L-Dopa + carbidopa-induced increase in LA in both caffeine treated and control rats when those drugs were administered concomitantly with bicuculline or L-Dopa+carbidopa. These results suggest that (a) the GABAergic system has direct role in the regulation of LA, and (b) caffeine potentiates LA by antagonism of the adenosine receptor and activation of the dopaminergic system which, in turn, reduces GABAergic activity through the reduction of cholinergic system.     

Age-dependent improvement in passive avoidance learning of the young chick: Cholinergic mediation?

Studied cholinergic mediation of the age-dependent improvement in response suppression of the young chick by determining the performance of 144 Vantress?×?Arbor Acre 4-day-old chicks, pretreated with scopolamine (SCO), during passive avoidance (PA) and extinction testing. In Exp I, Ss were trained to keypeck for heat reward (prepunishment training), and then tested for PA learning under immediate, 2-sec-delayed, or no shock condition. Half of the Ss in each condition received saline injections before prepunishment training and .5 mg/kg SCO injections after training. The rest received .5 mg/kg SCO injections both before and after training. For Ss in both SCO groups, delaying shock onset resulted in significantly less response suppression than immediate response-contingent shock. In Exp II, 4-day-old Ss injected with saline or SCO were trained to keypeck for heat reward and then tested for resistance to extinction under response-contingent shock or nonshock conditions. Punishment decreased the number of extinction responses for both saline and SCO groups. Results indicte that the age-dependent improvement in response suppression of the young chick cannot be explained solely by a significant increase in central cholinergic functioning. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activity of aryl sulfatase A enzyme in patients with schizophrenic disorders

The effect of diazepam on locomotor activity was tested by measuring the number of crossings between two compartments of a toggle-floor box, in control mice (water drinking) and in mice receiving caffeine solution (0.5 g/I) instead of drinking water. In control mice, diazepam did not produce any significant change in total activity measured on the whole 60-min test, but animals showed phases of increased activity broken by periods of immobility. After chronic ingestion (18 days) of caffeine, doses of 0.5, 1 and 2 mg/kg ip diazepam significantly increased total locomotor activity. Caffeine slightly reduced diazepam-induced immobility and increased the frequency of crossings in active periods. Taken together, these two effects may explain the significant increase in total activity induced by diazepam in caffeine-treated mice. Mixed stimulatory-depressant action was also produced by 3 mg/kg diazepam, a dose that slightly decreased the total activity.     

Antigen-specific immunoglobulin-A prevents increased airway responsiveness and lung eosinophilia after airway challenge in sensitized mice

The aim of this study was to examine the role of dopamine neurotransmission in the effects of morphine in the learned helplessness paradigm in rats, a generally recognized model of depression. In this model, rats first exposed to inescapable shocks (stressed rats) exhibited an escape deficit in a subsequent shuttle-box test performed 48 h later for 3 consecutive days. The numbers of escape failures and intertrial crossings (motor activity during each intertrial interval) were recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, s.c.), and haloperidol, a preferential D2-dopamine receptor antagonist, was injected i.p. 15 min before each shuttle-box session. At the highest dose tested (150 microg/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 microg/kg dose of haloperidol, which was ineffective by itself, reversed the morphine-induced improvement of escape behavior in previously stressed rats and the morphine-induced increase in intertrial activity in both stressed and nonstressed animals. These results support roles (a) for a dysregulation of dopaminergic neuronal activity in the expression of escape deficit subsequent to an inescapable aversive situation, and (b) for a dopaminergic mediation in the effects of morphine in the learned helplessness paradigm.     

Cholinergic drug effects on a delayed conditional discrimination task in the rat

The centrally acting cholinergic antagonist scopolamine (0.025-0.10 mg/kg ip) and the peripherally acting cholinergic antagonist methyl-scopolamine (0.01-0.10 mg/kg) dose dependently impaired discriminability independent of delay in a delayed conditional discrimination task that precludes use of mediating behavior. This indicates that scopolamine does not specifically affect working memory. Drugs that enhance cholinergic transmission neither improved discriminability nor attenuated scopolamine-induced impairments. In a post hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner in rats that performed at a high level in pretest sessions. Methyl-scopolamine impaired performance independently of delay in these rats. The authors suggest that a ceiling effect at short delays produced this Drug x Delay interaction of scopolamine in the best performing rats.