Trifluoperazine dihydrochloride (2.8–4.0 mg/kg/day) was administered continuously to rats in drinking water for six months. Animals killed at this time exhibited an increase in the number of dopamine receptors in the striatum and mesolimbic area, with a corresponding decrease in affinity (increase in the dissociation constant) for 3H-spiperone binding. In frontal cortex, 3H-spiperone binding to 5-HT receptors indicated no apparent change in numbers of receptors, but a slight increase in the dissociation constant. There was no obvious alteration in 3H-apomorphine binding in the striatum and mesolimbic area, but the individual results were very variable. The number and binding affinity of muscarinic receptors in striatum, mesolimbic area and cerebral cortex as identified by 3H-dexetemide were unchanged. Nor was there any alternation in the number or binding affinity of H-1 receptors identified by 3H-mepyramine, or of α-noradrenergic receptors identified by 3H-WB 4101, in cerebral cortex. The number and binding affinity of GABA receptors in the cerebellum identified by 3H-muscimol also was not altered.
Chronic neuroleptic administration to rats appears to alter specifically the number of cerebral dopamine receptors.