Dopamine receptors gene expression in male rat hippocampus after administration of MDMA (ecstasy) / La expresión génica de receptores de dopamina en el hipocampo de ratas macho después de la administración de MDMA (éxtasis)

Ecstasy is one of the most popular amusing drugs among young people. Documents indicate some effects of Ecstasy on hippocampus and close relations between dopaminergic functions with reward learning. Therefore, the aim of this study was evaluation of the chronic effects of Ecstasy on memory in male Wistar rats and determination of dopamine receptors' gene expression in hippocampus. Forty adult male Wistar rats randomly distributed in five groups: Control, sham (received 1 ml/kg 0.9% saline) and three experimental groups were: Exp. 1 (2.5 mg/kg), Exp. 2 (5 mg/kg), and Exp. 3 (10 mg/kg) received MDMA intraperitoneally once every 7 days (3 times a day, 3 hours apart) for 4 weeks. Before the first injection animals trained in Shuttle Box memory and tested after the last injection. 24 hours after the final testing, brains of rats were dissected and hippocampus was removed and homogenized. After total RNA extraction and cDNA synthesis, expression of dopamine receptor genes in the hippocampus determined with Real-Time PCR. Our results showed that 2.5 and 5 mg/kg MDMA-treated groups had memory impairment. Also we found that MDMA increased the mRNA expression of dopamine receptors in hippocampus and the highest increase found in dopamine D1 receptors in the 5 mg/kg experimental group. We concluded that low doses of Ecstasy could increase Dopamine takers gene expression in hippocampus and disorder avoidance memory. But in high doses the increase in Dopamine takers gene expression was not as much as that in low doses and avoidance memory disorder was not observed.

El éxtasis es una de las drogas de diversión más populares entre los jóvenes. La investigación reporta algunos de los efectos del éxtasis sobre el hipocampo y la relación entre las funciones dopaminérgicas con la recompensa en el aprendizaje. El objetivo de este estudio fue la evaluación de los efectos crónicos del éxtasis en la memoria de ratas macho Wistar y la determinación de la expresión de genes receptores de dopamina en el hipocampo. Cuarenta ratas macho adultas fueron distribuidas al azar en cinco grupos: grupo control, simulado (a 1 ml/kg 0,9% de solución salina) y tres grupos experimentales: Grupo exp. 1 (2,5 mg/kg), Exp. 2 (5 mg/kg), y Exp. 3 (10 mg/kg) recibió MDMA vía intraperitoneal cada 7 días (3 veces al día, con 3 horas de diferencia) durante 4 semanas. Antes de la primera inyección los animales fueron entrenados en memoria Shuttle Box y examinados después de la última inyección. Veinticuatro horas después de la prueba final, los cerebros de las ratas fueron diseccionados, el hipocampo fue separado y homogeneizado. Después de la extracción total de ARN y síntesis de ADNc, la expresión de genes de los receptores de dopamina en el hipocampo fue determinado con PCR en tiempo real. Nuestros resultados mostraron que los grupos de 2,5 kg y 5 mg/MDMA tratados tenían deterioro de la memoria. Además, encontramos que la MDMA aumentó la expresión de ARNm de los receptores de dopamina en el hipocampo y el aumento mayor se observó en los receptores D1 de dopamina en el 5 mg/kg Grupo experimental. En conclusión, las dosis bajas de éxtasis podrían aumentar tomadores de expresión génica de la dopamina en el hipocampo y trastornos de la memoria. Sin embargo, en dosis altas el aumento de la expresión génica no mostró un aumento significativo, a diferencia de los resultados con dosis bajas, tampoco se observaron trastornos disociativos de memoria.

Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion: Role of renal monoamine-oxidase / Perfiles de secreción de dopamina renal en la expansión de volumen para regular diuresis y natriuresis: Rol de la monoaminoxidasa renal

Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats U DA V (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 ± 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 ± 0.35 to 1.1 ± 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early U DA V peak to 3.2±0.72 (p < 0.01) and though, U DA V increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.

La dopamina (DA) intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V) durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO) y decarboxilasa de aminoácidos aromáticos (AADC) en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control), IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v.) y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.). Se observó que en C la U DA V (ng/30min/100gPC) aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05), disminuyendo posteriormente. IMAO mostró un patrón de liberación similar pero significativamente mayor que C a los 30 min de expansión (32.5 ± 2.20, p < 0.05). En este grupo la actividad de MAO disminuyó de 8.29 ± 0.35 a 1.1 ± 0.03 nmol/mg tejido/hora y aumentaron la diuresis y natriuresis por sobre los controles. En BNZ, el pico de U DA V observado a los 30 min de la expansión disminuyó a 3.2 ± 0.72 (p < 0.01), aunque luego de 60 minutos fue mayor que en C. BNZ disminuyó tanto la diuresis como la natriuresis. Podemos concluir que al comienzo de la expansión de volumen se produce un pico de excreción de dopamina renal hacia la orina. La enzima MAO juega un rol fundamental en esta respuesta.

Advances in research of ketamine addiction mechanism / 法医学杂志

Ketamine is a phencyclidine derivative acting primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) excitatory glutamate receptors. As a common intravenous anaesthetic in clinic, it is also increasingly abused because of its hallucination and addiction effects. Based on the pharmacological and toxicologic characteristics of ketamine and the acknowledged addiction mechanism of other abused drugs, this article reviews the possible addiction mechanism of the ketamine in the aspects of its enhanced effects and reward systems, the anatomic structures, the related receptors and the individual differences.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Effects of dextromethorphan on dopamine dependent behaviours in rats.

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.

A reviewing for abusing of ketamine / 法医学杂志

Ketamine is a noncompetitive NMDA receptor antagonist and comes into being a new problem of drug abuse. It can cause a certain extent of hallucination, which makes ketamine be abused in the casinos. The paper reviews the pharmacological and toxicology characteristic of Ketamine, the possible physiological mechanism and the methods for detecting Ketamine abuse.

Evaluation of cognitive brain functions in caffeine users: a P3 evoked potential study.

Caffeine is one of the most widely consumed stimulant drugs of the modern world. It brings about a feeling of well-being, relaxation, increased alertness and concentration. Its effects have been studied on brain function and behavior using mood questionnaires, reaction time tests, memory tests, EEG and of late Event Related Potentials (ERPs). This study evaluates the response of caffeine on ERPs and Reaction Time (RT) using auditory "oddball" paradigm. Forty undergraduate medical students volunteered for the study and their ERPs and RT were recorded before and after 40 minutes of ingestion of caffeine. There was a non-significant decrease in latency of N1, P2, N2 and P3 and a significant decrease in Reaction Time after caffeine consumption. The amplitude of P3 showed a significant increase after intake of caffeine. The results of this study indicate that caffeine leads to facilitation of information processing and motor output response of the brain.

Animal models of tardive dyskinesia--a review.

Tardive dyskinesia is a serious motor side effect of long term neuroleptic therapy, with an unknown pathophysiological basis. The leading hypothesis of the pathophysiology of tardive dyskinesia includes dopamine receptor supersensitivity, GABAergic hypofunction, excitotoxicity and oxidative stress. Many preclinical models have been developed to identify the underlying pathological processes of tardive dyskinesia, but none has yet produced a parsimonious results. A wide range of animal models, viz. Homologous, analogous and correlational models have been developed to explore the pathophysiology of tardive dyskinesia. Vacuous chewing movements in rodents induced by chronic neuroleptic treatment is the most frequently employed model. As the existing models suffer from several phenomenological and methodological problems, development of new models, highly predictive of pathological basis of tardive dyskinesia can accelerate tardive dyskinesia research for the better understanding of the pathophysiological processes underlying the syndrome and for the discovery of new therapeutic targets for the treatment of tardive dyskinesia.

Involvement of dopamine receptors in diethylpropion-induced conditioning place preference

Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N= 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 + 39 vs 565 + 48s). Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg, sc) 10 min before DEP (15 mg/kg, ip) blocked DEP-induced CPP (418 + 37 vs 389 + 31 s) while haloperidol (0.5 mg/kg, ip), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 + 36 vs 536 + 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DEP.

Some behavioural effects of chloroquine in rats suggesting dopaminergic activation.

The effect of chloroquine on open-field behaviour, apomorphine induced stereotypies and haloperidol and pimozide-induced catalepsy was studied in rats. Chloroquine (2.5-10 mg/kg, ip) significantly increased the locomotion frequently of rats in the open-field and also markedly enhanced apomorphine (0.4 mg/kg, sc)-induced locomotion. Haloperidol (0.25 mg/kg, ip) antagonised the increased locomotion frequency produced by chloroquine (5 mg/kg, ip), apomorphine (0.4 mg/kg, sc) and chloroquine plus apomorphine. L-Dopa (50 mg/kg, sc) and benserazide (12.5 mg/kg, ip) plus L-Dopa (50 mg/kg,sc) significantly increased chloroquine (5 mg/kg, ip)-induced locomotion. SCH 23390 (0.2 mg/kg, sc) and sulpiride (30 mg/kg, ip), on the other hand, attenuated chloroquine (5 mg/kg, ip)-induced locomotion. Chloroquine (2.5-5 mg/kg, ip) elicited stereotyped behaviour in rats and significantly potentiated apomorphine (2 mg/kg, sc)-induced stereotypies. Haloperidol (0.25 mg/kg, ip) markedly reduced the stereotypies produced by both chloroquine (5 mg/kg, ip) and apomorphine (2 mg/kg, sc). Both chloroquine (2.5-10 mg/kg, ip) and apomorphine (0.4 mg/kg, sc) significantly delayed the onset and decreased the intensity of catalepsy induced by haloperidol (0.25mg/kg, ip) and pimozide (2mg/kg, ip) respectively. These findings indicate that chloroquine, in low doses, produces excitatory effects and that dopaminergic mechanisms may be involved in the observed effects of chloroquine.

Effect of apomorphine on swim stress-induced antinociception in mice

It is well established that stress can cause antinociception in experimental animals. Alternatively, a number of studies have implicated brain dopamine in the modulation of nociceptive mechanisms. The aim of this study was to investigate the possible role of apomorphine [D1/D2 agonist] in swim induced antinociception [SIA] in male mice. The results obtained show that, depending on the dose employed, the drug can have variable effects on SIA; while a low dose [0,025 mg/kg] of apomorphine potentiates SIA [P<0.01], a higher dose [1.0 mg/kg] leads to its attenuation [P<0.05]. Blockage of D1 receptors via Such 23390 [D1 antagonist] reverses the 1 mg/kg effect of apomorphine while sulpiride [D2 antagonist] prevents the potentiating effect of the lower apomorphine dose [P<0.01]. This together with the other results obtained, indicate that D2 activation via the lower apomorphine dose augments SIA, while D1 activation via the higher apomorphine dose has an attenuating effect upon stress induced antinociception

Serotonergic modulation of footshock induced aggression in paired rats.

Footshock induced aggression (FIA) was induced in paired rats and three paradigms of aggressive behaviour were recorded, namely, latency to fight (LF), total period of physical contact (TPP) and cumulative aggression scores (CAS). The effects of increasing or decreasing central serotonergic activity, by using a number of pharmacological agents with well defined effects on rat brain serotonin, were investigated on FIA and on FIA augmented by apomorphine, a dopamine receptor agonist. The results show that centrally administered serotonin, the serotonin precursor, 5-hydroxytryptophan administered with clorgyline, a selective MAO A inhibitor, quipazine, a serotonin receptor agonist, and fluoxetine, a selective inhibitor of neuronal re-uptake of serotonin, attenuated all paradigms of FIA and apomorphine induced potentiation of FIA. On the contrary, the other re-uptake inhibitor used, citalopram, appeared to have a dual effect and decreased LF and CAS, while increasing TPP. The serotonin synthesis inhibitor, p-chlorophenylalanine and the selective serotonin receptor (5-HT2) antagonist, ketanserin, augmented all paradigms of FIA per se and apomorphine induced augmentation of FIA. However, the other serotonin receptor antagonist used, metergoline, which blocks both 5-HT1 and 5-HT2 receptor subtypes, attenuated FIA per se but decreased only CAS in apomorphine induced increase in FIA. The data confirm the inhibitory effect of the central serotonergic system on aggressive behaviour and the inverse relationship existing between it and the central dopaminergic system in the modulation of FIA, as has also been confirmed in earlier biochemical investigations from this laboratory. The data has been discussed in the light of existing knowledge on serotonin receptor subtypes and the presence of modulatory serotonergic heteroreceptors on central dopaminergic neurones.

Concomitant D1 dopamine receptor activation (SKF 38393) unmasks D2 dopaminergic actions of B-HT 920 in mice.

The present study attempts to demonstrate D1/D2 dopamine (DA) receptor interactions during stereotyped behaviour in mice. B-HT 920 [2-amino-6-allyl-5, 6, 7, 8-tetrahydro-4H-thiazolo-(4, 5-d)-azepine] (0.05-1.0 mg/kg), a selective D2-DA agonist, induced mild per se stereotypy consisting mainly of sniffing and rearing responses. Apomorphine, a mixed D1/D2 agonist, also produced typical stereotypic response in mice. The stereotypic response of B-HT 920 was blocked by D2-DA antagonist, sulpiride (50 mg/kg). The effect of apomorphine was not influenced by co-treatment with SKF 38393. Simultaneous administration of B-HT 920 (0.1-0.5 mg/kg) with SKF 38393 (5 mg/kg), a selective D1-DA agonist, elicited dramatic increase in stereotyped behaviours in naive as well as in 24 hr reserpinised (2 mg/kg) mice. Co-treatment of apomorphine (0.5 mg/kg) with B-HT 920 (0.1, 0.25 mg/kg) also resulted in a clearly synergistic effect on stereotyped behaviour. These potentiated responses were reduced or blocked by haloperidol, a D2-DA antagonist. The data suggest that in presence of concomitant stimulation of D1-DA receptors. B-HT 920 exhibits full expression of postsynaptic D2-DA receptor mediated behavioural effects.

Changes in the sensitivities of dopamine receptors to chronic treatment with imipramine & haloperidol in rats.

Apomorphine induced locomotor activity was studied in Wistar rats treated with imipramine and haloperidol with the help of automated measuring devices. The control rats showed a biphasic response of hypomotility and sedation to low dose apomorphine, and hypermotility to high dose apomorphine. In chronic imipramine-treated rats, the hypomotility and sedative response to low dose apomorphine challenge was significantly attenuated (P less than 0.05), as compared to saline treated controls. A similar response was observed in the chronically haloperidol treated rats (P less than 0.01). However, there were no significant differences in motility responses to high dose apomorphine challenge between the control and experimental groups. These results suggest that presynaptic dopamine auto receptors may not be involved in mediating the loss of response to low dose apomorphine by chronic imipramine treatment. Imipramine being predominantly a monoamine uptake inhibitor and haloperidol a potent postsynaptic D-2 blocker, some indirect mechanisms may be involved in the loss of response to low dose apomorphine challenge.

Effects of single and long-term administration of sulpiride on open-field and stereotyped behavior of rats

1. The effects of single (3.0 to 180.0 mg/Kg) and long-term (up to 90.1 mg/Kg) administration of sulpiride on open-field and apomorphine-induced stereotyped behavior of rats were studied. 2. when animals were studied 30 min after ip sulpiride administration and rearing frequencies in the open-field or apomorphine effects were not modified in a dose-dependent and consistentway by the single sulpiride administration. 3. In relation to control values, a significant decrease im apomorphine-induced stereotyped behavior was observed when rats were injected with a single sulpiride dose 2.5, 5.0, 7.5 and 10.0 h before the dopaminergic agonist. 4. Withdrawal from long-term ip sulpiride administration (up to 90.0 mg/Kg per injection, twice daily for 57 days) induced a significant increase in all parameters of activity recorded in the open-field, and the responsiveness to apomorphine was also augmented in sulpiride-withdrawn rats. 5. These results suggest that sulpiride, a benzamide drug that differs from classic neuroleptic agents by producing fewer extrapyramidal side effects, also supersensitivity of central dopaminergic receptors

Role of dopaminergic system in opioid-induced cardiovascular responses in dogs.

A study was carried out to determine the involvement of dopaminergic system in opioid-induced cardiovascular responses in the dogs. The study population consisted of 32 mongrel dogs of either sexes. The results show that morphine given in small dose (2 mg/kg I.V.) causes significant fall in blood pressure. The results also show that there is involvement of dopaminergic system in opioid-induced vasomotor responses in dogs. Partial blockade of the parenterally induced hypotensive response of morphine by haloperidol given centrally induced hypotensive responses of morphine by haloperidol given centrally in doses, which are too low to be effective by the peripheral route, strongly favours the involvement of central dopaminergic system in the morphine-induced hypotensive responses. The results also show that the hypotensive response of morphine was almost completely blocked after naloxone pretreatment by central route.

Influence of dopaminergic receptor supersensitivity on anticonvulsant action of carbamazepine.

Dopamine (DA) receptor supersensitivity was induced in albino rats by haloperidol (5 mg/kg, ip day, for 18 days) and after 48 hr carbamazepine (CBZ) was administered in graded doses. The animals were subjected to Maximal Electroshock Seizures (MES) test, Minimal Electroconvulsive Threshold (MET) test and Pentylenetetrazole (PTZ)-induced convulsions test. Haloperidol pretreatment marginally increased the effect of CBZ against PTZ induced seizures, but not against electrically induced seizures (MES and MET tests).

Rem sleep deprivation in an experimental model of Parkinson's disease

Privaçäo de sono REM em um modelo experimental da doença de Parkinson. Investigaçäo prévia mostrou que ratos privados de sono (REM SD) mostram acentuaçäo de resposta a agonistas dopaminérgicos. As evidências indicam que essa açäo parece ser mediada por supersensibilizaçäo de receptores dopaminérgicos pós-sinápticos. Com base nisso, foi feita REM SD em ratos com modelo experimental da doença de Parkinson, nos quais foi feita lesäo eletrolítica bilateral de ambas as vias nigro-estriatais. Sete dias após a cirurgia os animais eram submetidos a REM SD por 72 horas. Imediatamente após o final deste período era feita observaçäo em campo aberto para a ambulaçäo, "rearing", "grooming" e latência. Em comparaçäo com ratos näo-privados foi observado aumento significativo na ambulaçäo e "rearing", resposta que reapareceu após um segundo período de REM SD, realizado 21 dias após a cirurgia. Estes dados, de melhora de dois parâmetros de modelo experimental da doença de Parkinson, sugerem que a privaçäo de sono pode ser útil nesta doença

Antagonism of bromocriptine-induced cage climbing behaviour in mice by the selective D-2 dopamine receptor antagonists, metoclopramide and molindone.

Bromocriptine (5-30 mg/kg, ip), 2 hr after administration, induced cage climbing behaviour in mice. Pretreatment with haloperidol, an antagonist of both D-1 and D-2 dopamine receptors, metoclopramide and molindone, the selective D-2 dopamine receptor antagonists, effectively antagonised bromocriptine-induced climbing behaviour. The results indicate that bromocriptine most probably induces climbing behaviour in mice by stimulating the postsynaptic striatal D-2 dopamine receptors.