Effects of acute and chronic administration of phencyclidine on the A 10 dopaminergic mesolimbic system: Electrophysiological and behavioral correlates

Abstract

Electrophysiological and behavioral methods were used to evaluate the effects of chronic exposure to phencyclidine (PCP, 5 mg/kg/day for 30 days) on ventral tegmental A 10 dopaminergic neurons and locomotor and ataxic behavior in the rat. Extracellular recordings from single neurons in the ventral tegmentum showed only minimal differences between rats chronically treated with either saline or PCP. A comparison of the rising portion of the cumulative dose-response curves indicated that the animals treated chronically with the drug required only 0.4 times more PCP than the controls to produce equivalent changes in neuronal firing rates. Also, the average maximum increase in activity in A 10 neurons, induced by PCP, was 43% in the drug-treated rats compared to 60% in the controls. Although these were moderate quantitative changes, a marked qualitative difference in the response of A 10 neurons to PCP was seen. Whereas PCP elicited a characteristic dose-dependent biphasic effect on the firing rates in the control group, the declining (inhibitory) component of the response was not present in the animals chronically treated with PCP. In parallel with the minimal electfophysiological changes, measurements of gross locomotor activity showed that the response to the thirtieth (30th) injection of PCP was virtually identical to that measured in the same animals following the first exposure. In contrast, however, the ataxia which accompanied the hyperactivity rapidly diminished over the course of treatment. It would appear, therefore, that chronic exposure to PCP did not substantially diminish the ability of PCP to activate the A 10 neurons, comprising the mesocorticolimbic dopaminergic systems. In fact, with long-term chronic use of PCP, larger doses may actually result in a greater degree of stimulation of midbrain dopaminergic neurons. This effect may partially underly the neurobiological mechanism by which chronic abuse of PCP can eventually lead to psychotic-like personality changes.