A rapid and simple behavioural screening method for simultaneous assessment of limbic and striatal blocking effects of neuroleptic drugs.
A simple and rapid screening method, where the ability of neuroleptic drugs to antagonise the abnormal pattern of exploration induced by a low dose of d-amphetamine in a 10 min test, was evaluated. The d-amphetamine 2 mg/kg pretreatment induced both an increased locomotion, thought to reflect an increased dopamine transmission in the nucleus accumbens, and weak stereotypies, thought to reflect an increased dopamine transmission in the neostriatum. Haloperidol, chlorpromazine and thioridazine blocked all ongoing behaviours while clozapine and sulpiride, regarded as causing less extrapyramidal side effects in the clinic, only antagonised the d-amphetamine induced locomotion. The findings support the notion that the common site of action for anti-psychotic drugs is blockade of dopamine receptors outside the neostriatum while the blockade of dopamine receptors within the striatum probably are related to the propensity of these drugs to induce the extrapyramidal side effects. It seems possible with this method to screen neuroleptic drugs for their relative potency in blocking limbic and striatal dopamine receptors simultaneously in one short experiment. The method might be used when new anti-psychotic drugs with low incidences of extrapyramidal side effects are sought for.
Ljungberg
T
T
Ungerstedt
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U
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D003913:Dextroamphetamine