Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission.
Buspirone is a novel anti-anxiety drug which has neither a benzodiazepine structure nor any other benzodiazepine-like properties. Since buspirone is known to block dopamine autoreceptors and increase dopamine metabolism, it was compared to classical antipsychotic drugs for subchronic and chronic effects on dopaminergic function. When continuously infused into rats at 1.0 mg/kg/day s.c. for 2 weeks there was a small diminution of striatal dopamine metabolism response to acute injection of buspirone, but haloperidol produced a normal increase in DOPAC concentrations. In contrast, infusion of 0.3 mg/kg/day of haloperidol caused a marked subsensitivity to both acute buspirone and haloperidol challenge. The data from 3 months of treatment with buspirone or trifluoperazine (3.0 or 1.0 mg/kg/day, respectively) added to the rats' drinking water yielded similar results. Also, there was no alteration of dopamine autoreceptor sensitivity or postsynaptic D2 receptor sensitivity in 3 month buspirone treated rats. Three months of trifluoperazine produced a 45% increase in striatal binding of 3H-spiperone, which was reversed by simultaneous administration of buspirone during the final 2 weeks of trifluoperazine treatment. These data indicate that buspirone in moderate doses, such as used for treating anxiety, should be free of extrapyramidal side-effects. The modulation of neuroleptic-induced increased D2 receptor binding reinforces the hypothesis that buspirone has a modulatory effect at an unknown site within the extrapyramidal system.
McMillen
B A
BA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001835:Body Weight; D002065:Buspirone; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014268:Trifluoperazine / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D011743:Pyrimidines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D014268:Trifluoperazine; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D002065:Buspirone; D004298:Dopamine