Cataleptic Activity Research Articles

Investigation of the synergistic effect of asenapine maleate with fluoxetine on ketamine induced behavioural effects and estimation of brain monoamine in rats

Asenapine maleate (ASM), a potent antipsychotic for schizophrenia, has low oral bioavailability due to Cytochrome P450-1A2 metabolism and has been linked to depression side effects. Aim of the study is to investigate the effect of Asenapine Maleate-Fluoxetine combination. By decreasing CYP1A2, FLX could boost the bioavailability and effectiveness of ASM while reducing its side effects. The increased immobility time in ASM with FLX treated group compared to disease control while rearing and ambulation activities were significantly higher in the ASM, FLX, and combination compared to the disease control group, grooming was significantly lower in the ASM-treated and in the combination compared to the disease group. The Dopamine is significantly decreased in FLX and ASM with FLX treated group, the 5-Hydroxytryptamine is higher in all other groups except disease control and the noradrenaline concentration was higher in the ASM and ASM with FLX compared to the disease control group. The ASM and FLX show synergistic action, after dose, there is substantial cataleptic activity due to dopamine receptor blockade in the nigrostriatal pathway, causing muscular stiffness. Further research is required to prevent catalepsy and excessive diabetes induction due to the combination of ASM and FLX.

Decreased muscle strength in adjuvant-induced rheumatoid arthritis animal model: A relationship to behavioural assessments

Rheumatoid arthritis (RA) is an autoimmune disorder with unknown aetiology. Patients suffering from RA face persistent pain due to joint inflammation, and tissue destruction. Behavioural phenotyping is an approach to target the role of different behavioural traits associated with disease progression. The study aimed to assess behavioural patterns associated with decreased muscle strength in the adjuvant-induced rheumatoid arthritis animal model. The study was conducted on male Albino Wister rats (n = 30) [Control, Vehicle, and Disease groups]. After taking ethical approvals RA was induced by complete Freund's adjuvant (CFA) intradermally base of tail. The weight of animals, macroscopic analysis of inflammatory signs, and arthritic scores were measured weekly. Grip strength, ganglia-based movement, cataleptic activity, and motor-coordination-related behaviours were assessed among the groups. Radiographs and spleen index assay were performed followed by data analysis using one-way and two-way ANOVA (Analysis of Variance). A significant decrease in weight and an increase in arthritic scores among the diseased group was observed. Behavioural analyses confirmed that diseased animals had significantly decreased grip strength and increased cataleptic activity with less motor coordination. Radiographic images and spleen index assay confirmed the pattern of RA. Therefore, it can be suggested that the development of the disease animal model is an effective approach to identifying the disease progression and associated behavioural changes. Moreover, this prepared laboratory animal model may be utilised for pathway analyses to understand the key role of immune regulators and genetic insight into molecular pathways associated with acute and chronic phases of RA.

PDE10A inhibitors stimulate or suppress motor behavior dependent on the relative activation state of the direct and indirect striatal output pathways.

The enzyme phosphodiesterase 10A (PDE10A) regulates the activity of striatal, medium spiny neurons (MSNs), which are divided into a behaviorally stimulating, Gs-coupled D1 receptor-expressing “direct” pathway and a behaviorally suppressant, Gi-coupled D2 receptor-expressing “indirect” pathway. Activating both pathways, PDE10A inhibitors (PDE10AIs) combine functional characteristics of D2 antagonists and D1 agonists. While the effects of PDE10AIs on spontaneous and stimulated behavior have been extensively reported, the present study investigates their effects on suppressed behavior under various conditions of reduced dopaminergic neurotransmission: blockade of D1 receptors with SCH-23390, blockade of D2 receptors with haloperidol, or depletion of dopamine with RO-4-1284 or reserpine. In rats, PDE10AIs displayed relatively low cataleptic activity per se. After blocking D1 receptors, however, they induced pronounced catalepsy at low doses close to those required for inhibition of apomorphine-induced behavior; slightly higher doses resulted in behavioral stimulant effects, counteracting the catalepsy. PDE10AIs also counteracted catalepsy and related behaviors induced by D2 receptor blockade or dopamine depletion; catalepsy was replaced by behavioral stimulant effects under the latter but not the former condition. Similar interactions were observed at the level of locomotion in mice. At doses close to those inhibiting d-amphetamine-induced hyperlocomotion, PDE10AIs reversed hypolocomotion induced by D1 receptor blockade or dopamine depletion but not hypolocomotion induced by D2 receptor blockade. It is concluded that PDE10AIs stimulate or inhibit motor behavior dependent on the relative activation state of the direct and indirect striatal output pathways.

Study of the protective effect of fortified wheat grass with cow urine in experimentally induced parkinsonism

Parkinson’s disease (PD) is neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta which innervates the dorsal striatum. Since the existing anti Parkinson’s drugs encountered many side effects and need for prolonged treatment including questionable efficacy in the treatment, may cause Parkinson related movement problems, hallucinations and orthostatic hypotension. These reasons force the area of research to find improved treatments which will counteract the side effects and the draw backs of the existing treatment. Herbal drugs having diversified uses are always an alternative option to the synthetic drugs which are well known for their side and adverse effects . Using haloperidol induced catalepsy and muscle rigidity in rats the effects of Fortified Wheat grass (FWG) were studied. Haloperidol was administered at a dose of 1mg/kg; Fortified wheat grass with cow urine was administered at doses 150mg/kg & 300mg/kg. In conclusion fortified wheat grass with cow urine at doses of 150 and 300 mg/kg exhibited significant anti cataleptic activity, significantly reversed the haloperidol inhibited locomotor activity, restored the changes in behavioral assessment like akinesia, immobility in haloperidol administered rats, reduced the haloperidol induced rigidity. The possibility of pharmacological interactions between haloperidol and fortified wheat grass with cow urine should be further investigated in my research work.

Influence of Haloperidol and Clozapine on Some Behavioral Effects in Rats

The experiments presented in the following paper aimed to investigate the influence of atypical antipsychotic clozapine (CLO, CAS 578-21-0) classified also as normothymic drug on spatial memory in rats in Morris water maze test. The study also investigated the probably occurring side effects (measuring cataleptic activity and motor coordination) following single and chronic administration of CLO compared to haloperidol (HAL, CAS 52-86-8), a conventional antipsychotic. All the tests were carried out on male Wistar rats. CLO 10 mg/kg was administered orally 30 min before the tests and HAL 0.15 mg/kg was administered orally 60 min before the tests. In the Morris test memory improvement only after chronic administration of CLO on the 7th and 14th day of treatment was observed, whereas after 14 days of HAL treatment spatial memory impairment was noted. CLO did not induce catalepsy after single as well as chronic administration, but administrated chronically induced a tendency for its occurrence. HAL evoked a strong cataleptic effect both after acute and chronic treatment. CLO had no impact on motor coordination in the chimney test except on day 14 when statistically significant impairments were observed. HAL disturbed motor coordination in rats after single as well as chronic administration. The wide and unique spectrum of receptor activity of CLO in comparison with HAL as well as some neurotransmitters' interactions may explain its usefulness in long-term therapy of bipolar affective disorder and schizoaffective disorder with co-occurred cognitive deficits.

Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the beta-lactam antibiotic, ceftriaxone, in mice

Recently, it has been indicated that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Furthermore, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids. Since cannabinoid tolerance is known to be similar to opioids, our purpose was to examine the effect of ceftriaxone on the development of tolerance to WIN 55,212-2, a cannabinoid agonist. The tail flick test, a rectal thermometer, and the ring test were used for evaluating the degree of tolerance to the analgesic, hypothermic, and cataleptic effects of WIN 55,212-2, respectively. Within one week, animals became completely tolerant to analgesic, hypothermic and cataleptic effects of WIN 55,212-2 (6mg/kg). Ceftriaxone, with its higher doses (100–200mg/kg), attenuated the development of tolerance to the analgesic and hypothermic effects of WIN 55,212-2, but had no effect on its cataleptic action. Dihydrokainic acid (10mg/kg), a GLT-1 transporter inhibitor, prevented this effect of ceftriaxone. Our results suggest that repeated treatment with ceftriaxone prevents the development of tolerance to the analgesic and hypothermic effects of cannabinoids, and GLT-1 activation appears to play a key role in this preventive effect of beta-lactam antibiotics.

Neuroleptics: relation between cataleptic and anti-turning actions, and role of the cholinergic system.

Neuroleptics: relation between cataleptic and anti-turning actions, and role of the cholinergic system.

Central nervous system effects of the essential oil of the leaves of Alpinia zerumbet in mice

Abstract Objectives Alpinia zerumbet, known in Brazil as colônia, is popularly used as a diuretic, antihypertensive, anti-ulcerogenic and sedative. Based on this, we have investigated the central effects of the essential oil isolated from A. zerumbet leaves. Methods Mice were treated once with 50 or 100 mg/kg of the essential oil, intraperitoneally, 30 min before being submitted to behavioural models of: locomotor activity (open-field), catalepsy, anxiety (elevated plus maze), depression (forced swimming test and tail suspension tests) as well as apomorphine-induced stereotypy. Key findings Results showed a dose-related decrease on locomotor activity and apomorphine-induced stereotypy. There was a decrease to the order of 55% of the grooming behaviour with both doses studied. The essential oil 100 mg/kg increased cataleptic activity (167%) and the immobility time in the forced swimming and tail suspension tests. Pretreatment with haloperidol (0.2 mg/kg, i.p.) alone also decreased locomotion, increased cataleptic activity and immobility time in the tail suspension test. No alterations in the elevated plus maze test were registered. Conclusions The essential oil of A. zerumbet leaves had depressant and possible antipsychotic activity, since it could reverse the stereotypy induced by apomorphine, presenting effects comparable with those obtained with haloperidol treatment.

Central nervous system effects of the essential oil of the leaves of <I>Alpinia zerumbet</I> in mice

Alpinia zerumbet, known in Brazil as colônia, is popularly used as a diuretic, antihypertensive, anti-ulcerogenic and sedative. Based on this, we have investigated the central effects of the essential oil isolated from A. zerumbet leaves. Mice were treated once with 50 or 100 mg/kg of the essential oil, intraperitoneally, 30 min before being submitted to behavioural models of: locomotor activity (open-field), catalepsy, anxiety (elevated plus maze), depression (forced swimming test and tail suspension tests) as well as apomorphine-induced stereotypy. Results showed a dose-related decrease on locomotor activity and apomorphine-induced stereotypy. There was a decrease to the order of 55% of the grooming behaviour with both doses studied. The essential oil 100 mg/kg increased cataleptic activity (167%) and the immobility time in the forced swimming and tail suspension tests. Pretreatment with haloperidol (0.2 mg/kg, i.p.) alone also decreased locomotion, increased cataleptic activity and immobility time in the tail suspension test. No alterations in the elevated plus maze test were registered. The essential oil of A. zerumbet leaves had depressant and possible antipsychotic activity, since it could reverse the stereotypy induced by apomorphine, presenting effects comparable with those obtained with haloperidol treatment.

Behavioral Effects of the Novel CannabinoidSAAB-38-7 in Mouse Tetrad Assay

The Cannabis plant contains about 60 different cannabinoids, including the psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC). While the pharmacological actions of Δ9-THC have been extensively studied, other cannabinoid constituents have been largely neglected [1]. A recent interest in these compounds has emerged following the reported pharmacological interaction between cannabidiol (CBD) and Δ9-THC. Such interaction may have implications for understanding the long term consequences of marijuana users as well as the development of therapeutic uses for cannabis constituents. The current study evaluated the modulatory effect of a novel cannabinoid (SAAB-38-7) on Δ9-THC-induced hypolocomotion, catalepsy, hyperthermia, and antinociception, using the well established cannabinoid activity model (tetrad), as compared to the actions of CBD. In agreement with previous findings, at a dose of 100 mg/kg, CBD significantly (p < 0.05) antagonized the cataleptic action of Δ9-THC (20 mg/kg, i.p.) while it had no effect on the hypolocomotive, hypothermic, or antinociceptive actions. Compound SAAB-38-7 demonstrated a dose-dependent reduction of Δ9-THC-induced activity in the tetrad assay. Similar to CBD, compound SAAB-38-7 (10–40 mg/kg, i.p.) did not affect locomotor activity, catalepsy immobilization, rectal temperature, or nociception on its own. The collective data hence suggest a potential cannabinoid antagonist action of compound SAAB-38-7. Further characterization of such action is currently underway. Acknowledgements: The project described was supported by Grant Number P20RR021929 from the National Center For Research Resource and by the National Institute on Drug Abuse, contract # N01DA-5-7746.

The effect of nitric oxide on fentanyl and haloperidol-induced catalepsy in mice *

This study was designed to investigate the role of nitric oxide on catalepsy induced by fentanyl and haloperidol. Male albino mice were treated either with fentanyl (0.1-0.2 mg kg-1, s.c.) or haloperidol (0.5-2 mg kg-1, i.p.). The non-selective nitric oxide synthase inhibitor, NG-nitro-L-arginine (10 mg kg-1, i.p.), selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole (3 mg kg-1, i.p.), and nitric oxide donors, L-arginine (30-300 mg kg-1, i.p.) and D-arginine (30 mg kg-1, i.p.), were applied 20 min prior to fentanyl or haloperidol injection. A mu-opioid receptor antagonist naloxone (1 mg kg-1, i.p.) was also given in some groups. The cataleptic status of mice was assessed by placing animals in a rearing position in the cage. If the mouse maintained cataleptic posture for more than 20 s, it was scored as cataleptic and duration of catalepsy was expressed in terms of minutes. Both NG-nitro-L-arginine and 7-nitroindazole prolonged fentanyl-induced catalepsy (fentanyl: 3.6+/-0.8 min; fentanyl+NG-nitro-L-arginine: 77.4+/-14.6 min, fentanyl+7-nitroindazole: 56.0+/-10.4 min; n=6; P<0.01). This effect was reversed by L-arginine and naloxone, but not by D-arginine. Nitric oxide synthase inhibitors also prolonged the cataleptic action of haloperidol but to a lesser extent (haloperidol: 72.0+/-6.3 min; haloperidol+NG-nitro-L-arginine: 98.5+/-6.3 min, haloperidol+7-nitroindazole: 89.6+/-2.2 min; n=6; P<0.05). The prolongation of haloperidol-induced catalepsy with nitric oxide synthase inhibitors was not reversed by L-arginine. These results suggest a common mechanism between mu-opioid receptors and the nitric oxide system in the development of fentanyl-induced catalepsy in mice different from haloperidol-induced catalepsy.

Absence of tolerance to cataleptic activity of gamma-hydroxybutyric acid after subchronic administration to male mice

The number of silver-stained nucleolar organizer regions (Ag-NORs) was counted in stromal myofibroblasts in 125 cases of breast cancer. The mean (S.E.) of Ag-NORs in stromal myofibroblasts was 4.4 (0.1). The number of Ag-NORs in myofibroblasts was related to histological grade (p = 0.028), histological type (p = 0.013), tumour necrosis (p = 0.026), mitotic frequency (p = 0.091) and S-phase fraction (p = 0.032). The number of Ag-NORs in stromal myofibroblasts predicted survival with a borderline significance (x2 = 3.4, p = 0.052) and also in axillary lymph node negative tumours (X2 = 2.8, p = 0.095). The recurrence-free survival in the entire cohort (X2 = 7.1, p = 0.0075) and in axillary lymph node negative tumours (X2 = 7.1, p = 0.0078) could be predicted on the basis of the number of Ag-NORs in stromal myofibroblasts. In axillary lymph node positive tumours the number of Ag-NORs in stromal myofibroblasts had no prognostic value. In multivariate analysis the number of Ag-NORs in stromal myofibroblasts had no independent prognostic value.The results suggest a close interaction between stromal myofibroblasts and epithelial cancer cells in breast cancer, and stromal changes are clearly a subject for further analyses.

Differential response of cortical–limbic neuropotentiated compulsive mice to dopamine D 1 and D 2 receptor antagonists

We previously created transgenic mice in which dopamine D 1 receptor-expressing (D1+) neurons in regional subsets of the cortex and amygdala express a neuropotentiating cholera toxin (CT) transgene. These `D1CT' mice engage in complex biting, locomotor and behavioral perseverance–repetition abnormalities that resemble symptoms of human compulsive disorders associated with cortical–limbic hyperactivity. Because excessive cortical–limbic stimulation of striatal motor pathways may play a critical role in causing compulsive disorders, we examined the responsiveness of D1CT mice to dopamine D 1 and D 2 receptor antagonists. D1CT mice were found to be largely resistant to the cataleptic action of the D 1 receptor antagonist SCH23390. The abnormal repetitive leaping of D1CT mice was similarly unaffected by SCH23390. In contrast, the D1CT mice displayed supersensitivity to cataleptic induction by the D 2 receptor antagonist sulpiride. These data are consistent with the hypothesis that complex compulsions are mediated by chronic excessive corticostriatal (and/or amygdalostriatal) glutamatergic stimulation of the striatal direct and indirect motor pathways.

Effect of serotonergic agents on adenosine A2 receptor mediated catalepsy in mice.

The effect of serotonergic agents was studied on the adenosine A2 receptor agonist NECA-induced catalepsy in mice. The 5-HT releaser fenfluramine, the 5-HT1A agonist 8-OH-DPAT, the 5-HT(2A/1C) receptor agonist DOI and the 5-HT(2A/1C) receptor antagonists ketanserin and mianserin reversed NECA-induced catalepsy. p-MPPI and ketanserin reversed the anticataleptic actions of 8-OH-DPAT and DOI, respectively. Further, the 5-HT reuptake inhibitor fluoxetine, the 5-HT(1B/1C) receptor agonist TFMPP, the 5-HT synthesis inhibitor p-CPA, the selective 5-HT1A receptor antagonist p-MPPI, the 5-HT(1A/1B) receptor antagonist pindolol and the 5-HT3 receptor antagonist LY 278, 584 had no effect on NECA-induced catalepsy. The anticataleptic action of fenfluramine was not affected by pretreatment with p-CPA. In p-CPA treated rats, ketanserin did not affect the anticataleptic effect of fenfluramine, whereas p-MPPI partially reversed this effect. It is concluded that modulation of serotonergic neurotransmission at 5-HT1A and 5-HT(2A/1C) receptors affects the cataleptic action of experimental antipsychotic agents with adenosine A2 receptor agonistic activity.

A role of nitric oxide in WIN 55,212-2 tolerance in mice.

The role of nitric oxide (NO) in the development of cannabinoid tolerance was examined by using N(omega)-nitro-L-arginine methyl ester (L-NAME) as an inhibitor of NO synthase. R(+)-[2,3-Dihydro-5-methyl-3 [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-napht halenyl)methanone mesylate (WIN 55,212-2), a cannabinoid receptor agonist, or L-NAME plus WIN 55,212-2 was acutely or chronically injected i.p. to mice and analgesia, body temperature and immobility were measured. A single injection of WIN 55,212-2 induced time- and dose-dependent analgesia, hypothermia and catalepsy. L-NAME (50 mg/kg), which per se was ineffective, administered 20 min before WIN 55,212-2 did not modify the analgesic, hypothermic and cataleptic responses to the cannabinoid. When WIN 55,212-2 was administered once a day, the animals became completely tolerant to the analgesic, hypothermic and cataleptic effects within five, seven and nine days respectively. L-NAME injected once daily 20 min before WIN 55,212-2 inhibited the development of tolerance to the hypothermic and cataleptic actions but not to the analgesic action of WIN 55,212-2. Since L-NAME given chronically by itself did not modify the analgesia, hypothermia and catalepsy induced by acute administration of WIN 55,212-2, our findings suggest L-NAME acts with some selectivity on the mechanisms involved in cannabinoid tolerance.

The dopamine D 3 receptor antagonist, (+)-S 14297, blocks the cataleptic properties of haloperidol in rats

In contrast to haloperidol, the selective dopamine D 3 receptor antagonist, (+)-S 11566 {(±)-[7-( N, N-dipropylamino)-5,6,7,8-tetrahydro-naphtho(2,3 b)dihydro,2,3-furane]} and its active isomer, (+)-S 14297, induced neither catalepsy nor reduced conditioned avoidance responses in rats. (+)-S 11566 and (+)-S 14297 did, however, dose-dependently abolish the cataleptic actions of haloperidol. This action was expressed stereospecifically inasmuch as (−)-S 17777, the inactive distomer of (+)-S 14297, was ineffective. Further, the influence of haloperidol upon conditioned avoidance responses was not affected by (+)-S 14297. These data suggest that blockade of dopamine D 3 receptors may inhibit the extrapyramidal but not – as based on the conditioned avoidance response paradigm – antipsychotic actions of neuroleptics. © 1997 Elsevier Science B.V. All rights reserved.

Behavioural assessment in rats of the antipsychotic potential of the potent dopamine D 2 receptor antagonist, (-)eticlopride

The effects of the selective D 2 DA receptor antagonist, (-)eticlopride, a drug belonging to the benzamide class, were investigated on the D 2 DA agonist SND 919- and CQP 201–403-induced stereotyped behaviour and on CQP 201–403-induced shaking, in rats, and on isolation-induced aggression, in mice. (-)Eticlopride was also tested over a wide dose range (52–1200 μg kg −1, s.c.) for sedative and cataleptic activity, in rats. For comparison, some experiments were performed with (-)sulpiride (10 and 40 mg kg −1, s.c.) The data obtained show that (-)eticlopride differs from (-)sulpiride and potentially modifies animal behaviour, whether spontaneous or induced; moreover, they suggest a potential clinical use for this neuroleptic in the management of psychotic states.

Lesions of mouse striatum induced by 6-hydroxydopamine differentially alter the density, rate of synthesis, and level of gene expression of D1 and D2 dopamine receptors.

To study the effects of altering dopaminergic input on the levels and rate of synthesis of dopamine receptors, corpora striata of mice were lesioned unilaterally with 6-hydroxydopamine (6-OHDA), and the densities and levels of the mRNAs for D1 and D2 dopamine receptors were determined. The results showed that 6-OHDA caused significant reductions in D1 dopamine receptors and in D1 dopamine receptor mRNA in dorsolateral and dorsomedial regions of the lesioned striatum. By contrast, 6-OHDA lesions caused significant increases in D2 dopamine receptors and in D2 dopamine receptor mRNA in dorsolateral and ventrolateral regions of the lesioned striatum. To assess the effects of 6-OHDA lesions on the rate of synthesis of D1 and D2 dopamine receptors, the irreversibly acting dopamine receptor antagonist 2-ethoxy-1-ethoxycarbonyl-1,2- dihydroquinoline (EEDQ) was administered, and the rate of recovery of these receptors determined. The lesions decreased the rate of synthesis of D1 dopamine receptors in dorsolateral striatum but increased the rate of synthesis of D2 dopamine receptors in dorsolateral striatum. Correlation of these molecular events with dopaminergic behaviors showed that the rate of recovery from EEDQ-induced cataleptic activity and the recovery from inhibition of quinpirole-induced rotational behavior was more rapid than the recovery of either the D1 or D2 dopamine receptor. These results suggest that dopaminergic denervation differentially affects the rate of synthesis of D1 and D2 dopamine receptors in mouse striatum, and that these alterations in the rates of synthesis of the receptors may be explained by corresponding alterations in the levels of the respective transcripts for these receptors.

G-protein mediation of cannabinoid-induced phospholipase activation

The release of arachidonic acid from mouse peritoneal and S49 cells induced by Δ 1-tetrahydrocannabinol was found to be altered by prior exposure of the cells to either pertussis toxin or cholera toxin. The stable analogs of GTP and GDP, GTP-γ-S and GDP-β-S, were also effective in changing the extent of arachidonate release in saponin-treated cells. GDP- β-S essentially abolished the THC response, while GTP- γ-S showed effects mainly on vehicle-treated cells. The cataleptic action of THC in intact mice which is mediated by eicosanoids was also attenuated by pertussis toxin pretreatment. It is suggested that the THC receptor is coupled to phospholipases through one or more G-proteins and that adenylate cyclase probably does not have a role in this mechanism.

The ontogeny of SCH 23390-induced catalepsy in male and female rats exposed to ethanol in utero

The maturation of sensitivity to the cataleptic actions of selective D1 dopamine receptor blockade was assessed in rats exposed prenatally to ethanol, Pregnant rats received an average of 12.68 g/kg body weight of ethanol per day through a liquid diet. Control dams were either pair-fed an isocaloric liquid diet without ethanol or given ad lib lab chow. Separate groups of male and female offspring of these dams were administered either 0.33 or 1.00 mg/kg of the selective dopamine D1 receptor antagonist SCH 23390 at postnatal days 13, 17 or 21, and catalepsy was measured 0, 15 and 30 min later. The results are consistent with a hypothesis that prenatal ethanol exposure alters behaviors mediated by nigrostriatal dopamine systems. Overall, prenatal ethanol-exposed animals showed less catalepsy than control rats. Further, there is a gender effect in that dopamine antagonist-induced catalepsy matures earlier in normal male than in normal female controls. Prenatal alcohol exposure appears to delay the emergence of mature behavioral responses to dopamine blockade in male but not female rats.