Effects Of Dopamine Receptor Antagonists Research Articles

Dopamine D1-like receptor activation decreases nicotine intake in rats with short or long access to nicotine.

The use of nicotine and tobacco products is highly addictive. The dopaminergic system plays a key role in the initiation and maintenance of nicotine intake. Dopamine D1-like receptor blockade diminishes nicotine intake in rats with daily short (1h) access to nicotine, but little is known about the effects of dopamine receptor antagonists or agonists on nicotine intake in rats with intermittent long (23 h) access. Because of the extended access conditions and high nicotine intake, the intermittent long access procedure might model smoking and vaping better than short access models. We investigated the effects of the dopamine D1-like receptor antagonist SCH 23390 and the D1-like receptor agonist A77636 on nicotine intake in male rats with intermittent short or long access to nicotine. The rats self-administered nicotine for 5days (1h/day) and were then given 15 intermittent short (1h/day) or long (23 h/day) access sessions (3 sessions/week, 0.06 mg/kg/inf). The D1-like receptor antagonist SCH 23390 decreased nicotine intake to a similar degree in rats with short or long access to nicotine. The D1-like receptor agonist A77636 induced a greater decrease in nicotine intake in the rats with long access to nicotine than in rats with short access. Treatment with A77636 induced a prolonged decrease in nicotine intake that lasted throughout the dark and light phase in the long access rats. These findings indicate that blockade and stimulation of D1-like receptors decrease nicotine intake in an intermittent long access animal model that closely models human smoking and vaping.

Dopamine Receptor Antagonist‐Induced Elevation of the Compulsion Zone Results in Differential Effects on Cocaine Self‐Administration and Lever‐Pressing Behavior

Dopamine receptor antagonists raise both the cocaine priming and satiety thresholds (the lower and upper limits of the compulsion zone, respectively), so antagonists will decrease the probability of cocaine priming self‐administration behavior. However, if priming occurs in the presence of dopamine receptor antagonists, then cocaine consumption will accelerate. The compulsion zone also explains the lever‐pressing after access to cocaine is terminated, but the effects of antagonists on the compulsion zone are unexplored. The compulsion zone theory predicts that antagonists will decrease the duration of unloading activity. Male rats were trained to self‐administer cocaine on an FR1 schedule. Upon lever‐pressing, a unit dose (3 umol/kg i.v.) was administered. The dopamine receptor antagonists, SCH23390 (10‐30 nmol/kg), eticlopride (10‐30 nmol/kg), or molindone (750‐3000 nmol/kg) were administered i.v. either while cocaine was accessible during the maintenance phase or following termination of access denoting the start of the unloading phase. The lever‐pressing activity was recorded during the unloading phase. Antagonists accelerated self‐administration during the maintenance phase due to the elevated satiety threshold, consistent with previous studies. Antagonists administered immediately prior to the unloading phase shortened the duration of lever‐pressing, and lever‐pressing began at a higher calculated cocaine level. This is consistent with the antagonists elevating the compulsion zone. The faster elimination of cocaine at these elevated levels results in cocaine levels transiting the compulsion zone more rapidly. The differential effect of dopamine receptor antagonists on lever‐pressing behavior may provide insights to the appropriate use of antagonists as medications for cocaine use disorder.

Increased Risk of Parkinson's Disease in Patients With Schizophrenia Spectrum Disorders.

PD comorbid with schizophrenia has been considered rare because these diseases associate with opposite alterations in the brain dopamine system. The objective of this study was to investigate the risk of PD after a diagnosis of a schizophrenia spectrum disorder. Regionally, this was a retrospective record-based case-control study. The cohort included 3045 PD patients treated 2004-2019 in southwestern Finland. Nationally this was a nested case-control study using registers to examine Finnish patients who received a clinically confirmed PD diagnosis 1996-2015 (n=22,189). PD patients with previously diagnosed schizophrenia spectrum disorder (separate analysis for schizophrenia) were included. Comparable non-PD control groups were derived from both data sets. All PD diagnoses were based on individual clinical examinations by certified neurologists. In PD patients, the prevalence of earlier schizophrenia spectrum disorder was 0.76% in regional data and 1.50% in nationwide data. In age-matched controls, the prevalence in the regional and national data was 0.16% and 1.31%, respectively. The odds ratio for PD after schizophrenia spectrum disorder diagnosis was 4.63 (95% CI, 1.76-12.19; P < 0.01) in the regional data and 1.17 (95% CI, 1.04-1.31; P < 0.01) in the national data. Schizophrenia spectrum disorder increases the risk of PD later in life. This association was observed in both individual patient data and nationwide register data. Therefore, despite the opposite dopaminergic disease mechanisms, schizophrenia spectrum disorder increases rather than decreases the risk of PD. The increased PD risk could be related to risk-altering effects of dopamine receptor antagonists or to the increased vulnerability of the dopamine system induced by illness phase-dependent dopamine dysregulation in schizophrenia/schizophrenia spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Methylphenidate-Induced Oculogyric Crisis in a Patient with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Case Report

Methylphenidate is one of the agents used in the treatment of attention deficit hyperactivity disorder. In the literature, the following side effects were reported due to the use of methylphenidate: sleep and appetite problems, blood pressure and heart rate changes, headache, nervousness, crying, tics, chorea, psychosis, and rarely dystonic reaction. Acute dystonia is a well-known extrapyramidal side effect of dopamine receptor antagonists. The oculogyric crisis, a specific form of acute dystonic reaction, refers to usually upward and sometimes lateral deviation of the eyes for a certain period due to contraction of the extraocular eye muscles. Despite the increase in dopamine-related activity, psychostimulants were also reported to cause dystonic reactions rather than blocking. In this study, a patient with oculogyric crisis after the initiation of methylphenidate treatment was analyzed. Although rarely observed, dystonic reactions that may occur after methylphenidate should be considered by clinicians.

Imipramine administered before the first of two forced swim sessions results in reduced immobility in the second session 24 h later

A previous study investigating the effects of dopamine receptor antagonists administered before the first of two 24-h apart forced swim test (FST) sessions, provided evidence suggesting that evaluation of response efficacy – dependent on dopamine D2-like receptors – might play a role in setting the balance between active behaviours and immobility in this test. Regardless of the underlying mechanisms, the observation that the effects of drugs in the first session have consequences in the second session might be relevant for a better understanding of the FST in behavioural/functional terms. Thus, the first objective of this study was to investigate the consequences in the second session of the administration of the prototypic antidepressant drug imipramine before the first of two sessions. A second objective was to investigate the effect of dopamine D1-like and D2-like receptor blockade on the effects of imipramine. Imipramine (20 mg/kg) was administered 24-h, 6-h and 30-min before the first of two FST sessions performed 24-h apart. SCH 23390 (0.01, 0.04 mg/kg) or raclopride (0.0125, 0.25 mg/kg) were administered 30-min before the first session. Imipramine increased active behaviours both in the first and in the second session. Raclopride attenuated and SCH 23390 potentiated imipramine effects only in the first session and to a limited extent. These results show that imipramine administration before the first of two FST sessions induces an increase in active behaviours in the second session, and suggest that this effect is the consequence of the behavioural effects of imipramine in the first session.

Effects of chronic binge-like ethanol consumption on cocaine self-administration in rhesus monkeys

BackgroundMost cocaine abusers also abuse alcohol, but little is known about interactions that promote co-abuse. These experiments in rhesus monkeys determined the effects of >8 weeks of ethanol (EtOH) consumption on cocaine self-administration (n=6), effects of dopamine (DA) receptor antagonists on cocaine reinforcement (n=3–4 per drug) and the ability of the D2-like DA receptor agonist quinpirole to elicit yawning (n=3). MethodsMonkeys self-administered cocaine (0.0–1.0mg/kg/injection, i.v.) under a 300-s fixed-interval schedule and the above-listed variables were measured before EtOH exposure. Next, monkeys consumed a sweetened, 4% EtOH solution in the home cage under binge-like conditions: 1h, 5 days/week with daily intake equaling 2.0g/kg EtOH. After approximately 8 weeks, measures were re-determined, then EtOH drinking was discontinued. Finally, acute effects of EtOH on cocaine self-administration were determined by infusing EtOH (0.0–1.0g/kg. i.v.) prior to cocaine self-administration sessions (n=4). ResultsIn five of six monkeys, EtOH drinking increased self-administration of low cocaine doses but did not alter reinforcing effects of higher doses. Self-administration returned to baseline after EtOH access was terminated (n=3). Effects of DA receptor antagonists on cocaine self-administration were not consistently altered after EtOH consumption, but the ability of quinpirole to induce yawning was enhanced in two of three monkeys. Acute EtOH infusions only decreased self-administration of lower cocaine doses. ConclusionsTaken together, the data suggest that long-term EtOH exposure can increase sensitivity to cocaine, possibly by increasing D3 receptor sensitivity. Data do not support a role for acute pharmacological interactions in promoting cocaine/EtOH co-abuse.

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Studies support differential roles of dopamine receptor subfamilies in the rewarding and reinforcing properties of drugs of abuse, including ethanol. However, the roles these receptor subfamilies play in ethanol reward are not fully delineated. To examine the roles of dopamine receptor subfamilies in the acquisition of ethanol-induced conditioned place preference (CPP), we pretreated animals systemically with antagonist drugs selective for dopamine D1-like (SCH-23390) and D2-like (raclopride) receptors prior to ethanol conditioning trials. Effects of raclopride (0-1.2mg/kg) and SCH-23390 (0-0.3mg/kg) on the acquisition of ethanol-induced CPP were examined in DBA/2J mice (experiments 1 and 2). Based on significant effects of SCH-23390, we then determined if SCH-23390 (0.3mg/kg) produced a place preference on its own (experiment 3). To evaluate whether SCH-23390 impaired learning, we used a conditioned place aversion (CPA) paradigm and pretreated animals with SCH-23390 (0-0.3mg/kg) before conditioning sessions with LiCl (experiment 4). Whereas raclopride (0-1.2mg/kg) did not affect acquisition, SCH-23390 (0.1-0.3mg/kg) impaired the development of ethanol-induced CPP. SCH-23390 (0.3mg/kg) did not produce place preference when tested alone and SCH-23390 (0.1-0.3mg/kg) did not perturb the acquisition of LiCl-induced CPA. Our results support a role for dopamine D1-like but not D2-like receptors in ethanol's unconditioned rewarding effect as indexed by CPP. Blockade of D1-like receptors did not affect aversive learning in this procedure.

The D2 antagonist sulpiride modulates the neural processing of both rewarding and aversive stimuli in healthy volunteers

RationaleAnimal studies indicate that dopamine pathways in the ventral striatum code for the motivational salience of both rewarding and aversive stimuli, but evidence for this mechanism in humans is less established. We have developed a functional magnetic resonance imaging (fMRI) model which permits examination of the neural processing of both rewarding and aversive stimuli.ObjectivesThe aim of the study was to determine the effect of the dopamine receptor antagonist, sulpiride, on the neural processing of rewarding and aversive stimuli in healthy volunteers.MethodsWe studied 30 healthy participants who were randomly allocated to receive a single dose of sulpiride (400 mg) or placebo, in a double-blind, parallel-group design. We used fMRI to measure the neural response to rewarding (taste or sight of chocolate) and aversive stimuli (sight of mouldy strawberries or unpleasant strawberry taste) 4 h after drug treatment.ResultsRelative to placebo, sulpiride reduced blood oxygenation level-dependent responses to chocolate stimuli in the striatum (ventral striatum) and anterior cingulate cortex. Sulpiride also reduced lateral orbitofrontal cortex and insula activations to the taste and sight of the aversive condition.ConclusionsThese results suggest that acute dopamine receptor blockade modulates mesolimbic and mesocortical neural activations in response to both rewarding and aversive stimuli in healthy volunteers. This effect may be relevant to the effects of dopamine receptor antagonists in the treatment of psychosis and may also have implications for the possible antidepressant properties of sulpiride.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2278-4) contains supplementary material, which is available to authorized users.

S20-03 Determination of drug concentrations in serum and dopamine receptor occupancy in brain for optimal antipsychotic drug therapy

Evidence has been given that antipsychotic effects of dopamine receptor antagonists are associated with 60 and 80% striatal dopamine D2 and D3 receptor occupancy. Receptor occupancy correlates well with concentrations of the antipsychotic drugs in serum or plasma, much better than the dose. The latter is consistent with weak correlations between antipsychotic dose and serum concentrations and explained by the high interindividual variabilities in drug metabolism. Using positron emission tomography (PET) for in vivo determination of dopamine receptor occupancy in conjunction with drug concentration measurements “therapeutic windows” could be calculated for the atypical antipsychotic drugs amisulpride, risperidone and ziprasidone. On the other hand, analysis of drug concentrations in serum of schizophrenic patients who were treated with these drugs and who had responded to the medication confirmed the PET derived target levels and with some modifications also those of aripiprazole and clozapine. In vivo characterisation of dopamine receptor occupancy and measurement of blood levels should therefore be part of the clinical trials during the development of new antipsychotic drugs. They provide most relevant information for the later use of therapeutic drug monitoring to optimise the treatment of individual patients.

The effects of dopamine receptor antagonists on the activity of striatal neurons in rats during a probabilistic Pavlovian conditioning task

The effects of dopamine receptor antagonists on the activity of striatal neurons in rats during a probabilistic Pavlovian conditioning task

Morphine-induced antinociception in the formalin test: sensitization and interactions with D1 and D2 dopamine receptors and nitric oxide agents

In this study, the effects of dopamine receptor antagonists and nitric oxide agents on morphine-induced sensitization in the formalin test in mice have been investigated. Repeated daily intraperitoneal administration of morphine (30 mg/kg for 3 days) followed by a 11-day wash out period increased morphine-induced antinociception in the formalin test, which may be due to sensitization. The antinociceptive response to higher doses of morphine (6 and 9 mg/kg) but not 3 mg/kg was significantly increased in sensitized animals compared with control groups. Pretreatment of animals with an opioid receptor antagonist, naloxone (4 mg/kg), during repeated administration of morphine, attenuated the morphine-induced sensitization. In the second part of the study, the animals received SCH23390 (D1 receptor antagonist), sulpiride (D2 receptor antagonist), L-Arg (nitric oxide precursor) and NG-nitro-L-Arg methylester (nitric oxide synthase inhibitor) during repeated morphine administration, to evaluate the role of dopamine receptor antagonists and nitric oxide agents in this phenomenon. Pretreatment of animals with NG-nitro-L-Arg methylester (20 mg/kg) and sulpiride (100 mg/kg) during morphine sensitization decreased the antinociceptive response to higher doses of morphine in the formalin test. It is concluded that D2 dopamine receptor and nitric oxide mechanisms may be involved at least partly in morphine-induced sensitization in the formalin test.

Extinction of Cocaine Self-Administration Reveals Functionally and Temporally Distinct Dopaminergic Signals in the Nucleus Accumbens

While Pavlovian and operant conditioning influence drug-seeking behavior, the role of rapid dopamine signaling in modulating these processes is unknown. During self-administration of cocaine, two dopaminergic signals, measured with 100 ms resolution, occurred immediately before and after the lever press (termed pre- and post-response dopamine transients). Extinction of self-administration revealed that these two signals were functionally distinct. Pre-response transients, which could reflect the motivation to obtain the drug, did not decline during extinction. Remarkably, post-response dopamine transients attenuated as extinction progressed, suggesting that they encode the learned association between environmental cues and cocaine. A third type of dopamine transient, not time locked to overt stimuli, decreased in frequency during extinction and correlated with calculated cocaine concentrations. These results show that dopamine release transients involved in different aspects of cocaine self-administration are highly plastic--differentially governed by motivation, learned associations linked with environmental stimuli, and the pharmacological actions of cocaine.

Effects of Dopamine- and Serotonin-Related Compounds on Methamphetamine-Induced Self-Injurious Behavior in Mice

Methamphetamine induces hyperlocomotion, and high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. It is well known that the monoaminergic system is involved in methamphetamine-induced behavior. However, the effects of dopamine- and serotonin (5-HT)-related compounds on high-dose methamphetamine-induced behavior have not been sufficiently clarified. Therefore, the present study was designed to investigate the effects of dopamine receptor antagonists and indirect 5-HT receptor agonists on high-dose methamphetamine-induced behavior in mice. Methamphetamine (20 mg/kg) initially increased locomotor activity. As the dosage increased, continuous SIB accompanied by a reduction in locomotor activity was observed. The hyperlocomotion and SIB induced by 20 mg/kg of methamphetamine was abolished by high doses of SCH23390 and haloperidol, indicating that the hyperlocomotion and SIB induced by high doses of methamphetamine are mediated by the activation of D1- and D2-receptors. Furthermore, haloperidol (0.1 mg/kg) potently increased locomotor activity in combination with 20 mg/kg methamphetamine. These results suggest that excess dopaminergic activation, especially activation of dopamine D2-receptors, may be involved in the decrease in locomotor activity induced by a high dose of methamphetamine. On the other hand, indirect 5-HT receptor agonists attenuated methamphetamine-induced SIB, suggesting that the stimulation of 5-HT receptors plays an important role in high-dose methamphetamine-induced SIB in mice.

Potential for antipsychotic and psychotomimetic effects of A2A receptor modulation.

The discovery of antagonistic interactions between A2A adenosine receptors and D2 dopamine receptors in the ventral striatum suggested that A2A receptor activation might modulate the antipsychotic effects of dopamine receptor antagonists and could provide an opportunity for the development of A2A receptor agonists as novel antipsychotic drugs. However, there is limited evidence from preclinical and clinical studies that A2A receptor agonists can exert antipsychotic effects. Furthermore, it remains unclear whether A2A receptor agonists possess a sufficient safety margin or whether their potent hypotensive effects or extrapyramidal side effects would limit their therapeutic utility as antipsychotic agents. The interaction between A2A receptors and D2 receptors also raises the possibility that A2A receptor antagonists, which hold considerable promise as antiparkinsonian agents, may have dose-limiting psychotomimetic side effects. Preclinical studies using selective A2A receptor antagonists suggest that this class of compound has a low propensity to elicit psychotomimetic side effects or exacerbate those induced by D2 receptor agonists.

Mechanism of new antipsychotic medications: occupancy is not just antagonism.

Antagonism of D2-like dopamine receptors is the putative mechanism underlying the antipsychotic efficacy of psychotropic drugs. Positron emission tomographic studies suggest that the antipsychotic effect of dopamine receptor antagonists occurs within a therapeutic window between 60% and 80% (striatal) D2 receptor occupancy. The incidence of extrapyramidal side effects increases above the 80% threshold. However, the novel atypical antipsychotic drug, aripiprazole, occupies up to 95% of striatal D2-like dopamine receptors at clinical doses, and the incidence of extrapyramidal side effects with aripiprazole is no higher than with placebo. The most likely explanation for this finding is aripiprazole's weak partial agonism at D2-like dopamine receptors. This particular pharmacologic feature characterizes a new class of atypical antipsychotics that does not match the original concept of a therapeutic occupancy window for antagonist antipsychotics. When not involving pure antagonists, it implies a need to adjust the expected receptor occupancy (measured using positron emission tomography) for the therapeutic window.

INTERACTIVE EFFECTS OF ACUTE AND CHRONIC LITHIUM WITH DOPAMINE RECEPTOR ANTAGONISTS ON NALOXONE-INDUCED JUMPING IN MORPHINE-DEPENDENT MICE

In the present study, interactive effects of D1 and D2 dopamine receptors antagonists and different periods of lithium pretreatment on morphine dependence in mice have been investigated. This study was designed to investigate whether the hypothesis that lithium and dopaminergic mechanisms via their effects on phosphoinositide pathways and calcium flux could influence morphine withdrawal response as manifested in the jumping effect. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 a.m., 1 p.m. and 4 p.m.) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the 4 th day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2h after the last dose of morphine. To study interactive effects of dopamine receptor antagonists and different duration of lithium pretreatment, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. SCH 23390 (0.01, 0.02 and 0.05 mg/kg) as a D1 dopamine receptor antagonist and sulpiride (20, 40 and 80 mg/kg) as a D2 dopamine receptor antagonist were able to prevent withdrawal signs precipitated by naloxone (5 mg/kg). Pretreatment of animals with lithium (600 mg/l) for 7, 14, 21 and 28 days, increased jumping induced by naloxone in morphine dependent animals. SCH 23390 did not show any significant alteration on the jumping response in animals pretreated with lithium for 28 days, but the inhibitory effects of sulpiride was significantly decreased in animals received lithium for 28 days. It is concluded that postreceptor mechanism (s) may be involve in the interactions of lithium with dopaminergic system in alteration of naloxone-induced jumping in morphine dependent animals.

Effects of dopamine receptor antagonists on nicotine-induced attentional enhancement.

An understanding of the neuropharmacological mechanisms mediating attentional enhancement by nicotine would indicate whether these effects could be dissociated pharmacologically from other behavioural effects of nicotine. The aim of the present study was to examine the involvement of dopamine neurotransmission in the effects of nicotine on different response indices of an attentional paradigm. The effects of the D2-type dopamine receptor antagonist raclopride (0.025-0.1 mg/kg) and the D1-type receptor antagonist SCH23390 (0.006-0.024 mg/kg) were tested, in both the presence and absence of nicotine (0.1 mg/kg), in rats trained in a modified version of the five-choice serial reaction time task (5-CSRTT). Nicotine robustly enhanced the accuracy of signal detection, reduced omission errors and shortened response latencies. Neither raclopride nor SCH23390 altered the effects of nicotine on accuracy and omissions, but raclopride augmented accuracy and SCH23390 increased omissions when given alone. By contrast, raclopride, but not SCH23390, reversed the nicotine-induced reductions in response latencies, at doses that had no effect on their own. In the presence of nicotine, both antagonists had rate-disruptive effects at the highest dose. Both antagonists also reduced responding in the intertrial interval, and this effect was additive to the nicotine-induced decrease in this measure. The data indicate that D2-type dopamine receptors may be involved in the effects of nicotine on response speed. Neither the D1- nor the D2-type dopamine receptor antagonist affected nicotine-induced improvements in signal detection, at doses that reversed dependence-related behavioural effects of nicotine in previous studies. Thus these effects may be pharmacologically dissociable.

Effect of Dopamine Receptor Antagonists on Renewal of Cocaine Seeking by Reexposure to Drug-associated Contextual Cues

We recently found that in rats trained to self-administer a heroin-cocaine mixture, exposure to the drug self-administration environment, after extinction of the drug-reinforced behavior in a different context, leads to renewal of drug seeking. Here we further explored the role of contextual stimuli in drug seeking by characterizing the effect of drug-associated environmental stimuli on renewal of cocaine seeking. We also investigated whether activation of dopamine receptors contributes to context-induced renewal of cocaine seeking by testing the effects of selective D1-like (SCH 23390) and D2-like (raclopride) receptor antagonists. Rats were trained for 10 days to self-administer cocaine by pressing a lever. Next, lever pressing was extinguished in the presence of the discrete cues associated with cocaine infusions for 10 days in a context that was distinctively different from the drug-taking context. On the test days, rats were pretreated with SCH 23390 (0, 5 or 10 μg/kg) or raclopride (0, 50 or 100 μg/kg) and non-reinforced lever-pressing behavior was determined either in the extinction context (Control group) or the cocaine-associated context (Renewal group). Consistent with our previous report, cocaine seeking was renewed when rats were exposed to the drug-associated context after extinction in a different context. Furthermore, pretreatment with the D1-like or the D2-like receptor antagonists attenuated context-induced renewal of cocaine seeking. These data suggest that activation of dopamine receptors is involved in reinstatement of cocaine seeking induced by exposure to the drug self-administration context.

Combined Treatment of Tourette Syndrome with Δ9-THC and Dopamine Receptor Antagonists

SUMMARY Animal studies suggest that cannabinoid receptor agonists might enhance the effect of dopamine receptor antagonists (neuroleptics, NL) in hyperkinetic movement disorders. In Tourette syndrome, NL are the most effective drugs for the treatment of tics. Recent clinical trials demonstrated that delta-9-tetrahydrocannabinol (Δ9-THC) also produces a tic-suppressing effect. In this single case study in a 24 years old female suffering from TS with extreme tics, it is suggested for the first time that Δ9-THC may be useful in augmenting the pharmacological response to atypical NL such as amisulpride and risperidone in TS patients. No serious adverse reactions occurred. Controlled studies are necessary to confirm this initial report.

Effects of dopamine receptor antagonists on ongoing maternal behavior in rats

The effects of different peripheral doses of four dopamine (DA) receptor antagonists on general activity and maternal behavior were examined in lactating female rats. Administration of the classic D1-like and D2-like DA receptor blocker haloperidol (0.1 and 0.05 mg/kg) disrupted pup retrieval and nest-building behaviors and reduced motor activity. Pimozide (0.5 and 0.2 mg/kg), which has more affinity for DA D2-like receptors, mildly disrupted pup retrieval while showing no significant influence on open-field behaviors. The putative DA D 4 receptor blocker, clozapine (1.5 and 1.0 mg/kg) reduced motor activity significantly, while only 1.0 mg/kg dose significantly decreased percent of rats displaying nest building. The DA D1-like receptor blocker SKF-83566 (0.2 and 0.1 mg/kg) significantly reduced pup retrieval, nest building and motor activity. These results suggest a role for DA receptors in ongoing maternal behavior that correlates directly with general activity.