Supersensitivity of dopamine-autoreceptors. The effect of gammabutyrolactone in long-term haloperidol treated rats.

Rats were injected daily with haloperidol, 0.5 mg/kg i.p. for a period of 16 days. 24 hours after the last injection of haloperidol these rats were challenged with gammabutyrolactone in doses of 200-750 mg/kg i.p. The ensuing increase in neostriatal dopa-accumulation was significantly lower than in rats not previously treated with haloperidol. Since the increase in dopa-accumulation following GBL-treatment is most probably independent of postsynaptically located DA-receptors the difference between the experimental series is explained in terms of reduced feedback activation of DA-synthesis due to the increased sensitivity of presynaptically located DA-autoreceptors.