The abuse of psychomotor stimulants, cocaine and amphetamine, is thought to involve the responses of postsynaptic neurons in the nucleus accumbens and striatum to facilitated dopaminergic transmission by these drugs. The behavioral manifestations of this effect appear to be differentially mediated by these two neuroanatomical locations. Most convincingly demonstrated thus far in rats, the nucleus accumbens is implicated mainly in mediating the locomotor and reinforcing effects of these drugs, and the striatum mainly in the effects of higher doses of psychomotor stimulants on stereotyped behavior (e.g., licking, repetitive head movement). This difference almost certainly involves our recent discovery that neurons in the lateral, but not medial, striatum of the rat fire in relation to sensorimotor activity of specific parts of the body. It is not yet clear how the activity of striatal and accumbens neurons might participate in mediating psychomotor stimulant-induced stereotypy and locomotion, respectively. To address this issue, we will record the responses of single neurons in these two areas to systemic injections of cocaine or amphetamine. The firing of lateral striatal neurons related specifically to head movement or licking will be characterized during these movements after saline injection (control) and after drug injection, when the drug is altering the frequency of these movements. Similarly, drug effects will be assessed on the firing rates of accumbens neurons in the context of the moss prominent motor behavioral correlate of this structure, locomotion. The relatively high degree of knowledge about the motor behavioral variables controlling the firing rate of a neuron, particularly in the case of a neuron related to a specific, measurable movement, increases the reliability of assessing drug effects on firing. Results of the new approach proposed here and pioneered in this laboratory have suggested that the transduction of psychomotor stimulant drug action into increased frequency of certain movements may involve elevated firing of striatal neurons related to those movements, which may act to bias target neurons in premotor areas to increase the likelihood of repeating those movements. Clarifying psychomotor stimulant effects on the firing of striatal neurons related to stereotyped movements can provide novel insights regarding the response of dopamine sensitive neurons to these drugs, which may pertain to their abuse. Moreover, in light of abundant evidence linking both the reinforcing and locomotor-stimulating effects of psychomotor stimulants to the nucleus accumbens, valuable information will be provided by clarifying the effects of these drugs on locomotor-related firing of accumbens neurons.
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