Antipsychotic substances and dopamine in the rat brain; behavioral studies reveal distinct dopamine receptor systems.
Graded doses of apomorphine were injected into terminal areas of the nigrostriatal, mesolimbic and mesocortical dopamine (DA) systems of the rat brain. Injection of high doses of apomorphine into the nucleus caudatus elicited stereotyped sniffing, but did not affect the motility of the rat. Low and high doses of apomorphine injected into the nucleus accumbens decreased and increased motility, respectively, without changing sniffing behavior. Injection of both low and high doses of apomorphine into the pyriform cortex increased sniffing behavior, but did not affect motility. All these apomorphine-induced behavioral responses were antagonized by local pretreatment with the typical neuroleptic, haloperidol, and the atypical neuroleptic, sulpiride, albeit with different potencies as revealed from the calculated ED50 values (ranging from 0.18-20,462 fmol). Local pretreatment with the antipsychotic peptide, des-enkephalin-gamma-endorphin (DE gamma E), antagonized the behavioral changes induced by injecting low and high doses of apomorphine into the pyriform cortex and low doses into the nucleus accumbens (ED50: 0.22-20.6 fmol), but did not affect the behavioral effects elicited by injecting high doses of apomorphine into the nucleus caudatus or the nucleus accumbens. It is proposed that two distinct types of DA receptor systems are present in the rat brain. These are characterized by the slope of the dose-response curve for the substances to antagonize the apomorphine-induced behavioral effects and by the effectiveness of DE gamma E in this respect. The antipsychotic effects of these compounds may be mediated by DA systems in the nucleus accumbens or in the pyriform cortex; this last system is especially sensitive to the three antipsychotic substances and is equally affected by them (ED50 value for the antagonism of the apomorphine-induced effects: 0.18-0.71 fmol).
Van Ree
J M
JM
Rudolf Magnus Institute of Pharmacology, Medical Faculty, State University of Utrecht, The Netherlands.
Elands
J
J
Király
I
I
Wolterink
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000033:anatomy & histology; D003342:Corpus Striatum / Q000033:anatomy & histology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000033:anatomy & histology; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D001615:beta-Endorphin; C033558:des-enkephalin-gamma-endorphin; D013469:Sulpiride; D001058:Apomorphine; D004298:Dopamine