Are antagonists of dopamine D1 receptors drugs that attenuate both positive and negative symptoms of schizophrenia? A pilot study in Java monkeys.
Amphetamine is known to elicit stereotyped behavior in various species. For a long time, this effect was considered to be an animal model for the positive symptoms of schizophrenia. In addition, amphetamine is known to induce a strong social isolation in socially living monkeys. Both on symptomatologic and pharmacologic grounds, this amphetamine-induced social isolation has been suggested to represent an animal model for the negative symptoms of schizophrenia. To date no effective treatment has been found for these negative symptoms. We now report that the selective D1 dopamine antagonist SCH 23390 is very effective in antagonizing both the stereotyped behavior and the social isolation in Java monkeys induced by amphetamine. Moreover, SCH 23390 is able to reinstate normal behavior in these animals. These results may have important consequences for our understanding of the functional significance of the D1 receptor as well as for the clinical treatment of the positive and negative symptoms of schizophrenia.
Ellenbroek
B A
BA
University of Nijmegen, Psychoneuropharmacology Research Unit, The Netherlands.
Willemen
A P
AP
Cools
A R
AR
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001552:Benzazepines / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008960:Models, Psychological; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D012016:Reference Values; D012559:Schizophrenia / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000187:drug effects*
D014150:Antipsychotic Agents; D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D003913:Dextroamphetamine