Comparison of the effects of chronic haloperidol treatment on A9 and A10 dopamine neurons in the rat.

The effects of chronic haloperidol (CHAL) treatment on A9 and A10 dopamine (DA) neurons were compared using extracellular single cell recording techniques. CHAL caused a time-dependent reduction in the number of spontaneously active A9 and A10 DA cells and induced an irregular firing pattern in many of the DA cells that remained active. Both of these effects occurred earlier and to a greater extent in A10 than in A9. Intravenous injection of the DA agonist apomorphine reversed both the reduction of active DA neurons and the irregular discharge pattern, suggesting that both effects were due to the process of depolarization inactivation. Lesions of the nucleus accumbens (NAc) produced by ibotenic acid prevented the development of depolarization inactivation of A10 DA neurons, indicating that this process is mediated primarily by NAc-A10 feedback pathways. The results suggest that the slow development of depolarization inactivation of DA cells produced by CHAL may contribute to the delayed onset of the clinical effects of long-term treatment with antipsychotic drugs.