Phencyclidine-induced activation of ventral tegmental A10 dopamine neurons is differentially affected by lesions of the nucleus accumbens and medial prefrontal cortex.
The nucleus accumbens and medial prefrontal cortex contain high concentrations of phencyclidine (PCP) binding sites as well as supply inhibitory and excitatory inputs to the ventral tegmental area (VTA). Thus these two regions could be instrumental in mediating the unique bimodal response of A10 neurons to systemically administered PCP. Therefore we evaluated electrophysiologically the effects of lesions of these two areas on this pattern of response. In sham-lesioned controls, i.v. injections of PCP elicited a typical dose-dependent bimodal effect which was characterized by an activation of A10 firing at low dose (reaching a maximum of +44% at 1 mg/kg) followed by a slowing of this response with larger doses. However, in animals with kainic acid or radiofrequency lesions of the nucleus accumbens, PCP produced only a unimodal response resulting in sustained and elevated (+88% in kainate and +55% in radiofrequency lesioned groups) firing rates. Notably, neither basal activity nor the degree of activation of the A10's at doses of PCP less than 1 mg/kg were affected by the lesions. In contrast, excitotoxic destruction of the medial prefrontal cortex had no effect on the response of A10 neurons to PCP even though basal activity was slightly elevated in this group. These results suggest that the inhibitory component of the bimodal response of VTA neurons to systemic PCP is mediated via feedback pathways from the nucleus accumbens, but that the mesocortical prefrontal cortex does not appear to modulate any portion of this bimodal response.
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Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.
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D000818:Animals; D004298:Dopamine / Q000502:physiology; D004594:Electrophysiology; D005625:Frontal Lobe / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000473:pathology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000473:pathology*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D010622:Phencyclidine; D004298:Dopamine