Cerebral dopamine function in rats following withdrawal from one year of continuous neuroleptic administration

European Journal of Pharmacology
A ClowC D Marsden

Abstract

Continuous administration of trifluoperazine (2.5--3.5 mg/kg/day) or thioridazine (30--40 mg/kg/day) to rats for 12 months enhanced the stereotyped response to apomorphine (0.5 mg/kg s.c.), increased dopamine 1--150 muM) stimulation of striatal adenylate cyclase, increased KD and Bmax for dopamine (10(-4) M) specific 3H-spiperone striatal binding and produced spontaneous mouthing movements. On drug withdrawal, spontaneous locomotor activity was enhanced after 2 weeks and the enhanced stereotyped response was maintained for up to 1 month. Spontaneous mouthing had disappeared 2 weeks after drug withdrawal. The increase in Bmax for 3H-spiperone binding was maintained for up to 3 months after drug removal, but KD reverted to control levels by 2 weeks. In contrast, the dopamine stimulation of striatal adenylate cyclase remained enhanced for the 6 month withdrawal period. Administration of trifluoperazine (0.7--0.9 mg/kg/day) or thioridazine (6--8 mg/kg/day) for 12 months produced a less marked effect than administration of the higher dose. No enhancement of effect was observed on drug withdrawal and the initial changes disappeared rapidly on removal of drug. Supersensitivity of striatal dopamine mechanisms produced by continuous lon...Continue Reading

References

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