title: Long-term behavioural and biochemical effects following prolonged treatment with a neuroleptic drug (flupenthixol) in rats.
abstract: The effects of long-term treatment (36 weeks) with a neuroleptic drug (flupenthixol) were investigated behaviourally and biochemically in rats. Sixteen rats were trained on a DRL (differential reinforcement of low rate) 15-s schedule until stable responding was obtained. During the following 36 weeks 9 rats were injected weekly with flupenthixol dissolved in Viscoleo [4 mg/kg(i.m.)] and seven rats received Viscoleo alone. During this period the animals were not run on the DRL schedule. Retesting on DRL 7 weeks after the last drug injection yielded highly significant differences between the flupenthixol-treated animals and the controls. Thorough neurological examinations of the animals just preceeding the retesting period also revealed some deficits in the flupenthixol-treated animals. At sacrifice, 14-18 weeks after the last drug injection, levels of homovanillic acid (HVA) were measured in the corpus striatum and total 3-methoxy-4-hydroxyphenylglycol (MOPEG) in the rest of the forebrain. The results indicate a nonsignificant increase of 25% in the dopamine metabolite HVA, while the noradrenergic metabolite MOPEG was significantly decreased by 14% in experimental animals. The possibility of persistent functional and biochemical effects produced by prolonged treatment with a neuroleptic drug is highlighted in the results presented here.
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005475:Flupenthixol / Q000494:pharmacology*; D006651:Histocytochemistry; D006719:Homovanillic Acid / Q000378:metabolism; D007837:Latency Period, Psychological; D008297:Male; D051381:Rats; D013892:Thioxanthenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D013892:Thioxanthenes; D005475:Flupenthixol; D006719:Homovanillic Acid