Increased binding potential of [11C]raclopride during unilateral continuous microinjection of nicotine in rat striatum observed by positron emission tomography

Abstract

Nicotine injections and nicotine skin patches significantly improve attention, memory, and learning in Alzheimer's disease. In animal studies, nicotine improves the performance of various memory-related tasks, an effect that is thought to be mediated by the neuronal dopaminergic system as systemic administration of nicotine decreased [(11)C]raclopride binding in the anesthetized state. Since high doses of systemically administered nicotine are harmful, we administrated it directly into the rat striatum via microdialysis. We then examined the acute effects of continuous central administration of high doses of nicotine on striatal dopamine concentrations by measuring [(11)C]raclopride binding by positron emission tomography. The concentration of dopamine in the dialysates was significantly increased from basal levels when microdialysis with 100 mM nicotine was initiated. However, contrary to expectations, the binding potential (BP) of [(11)C]raclopride in the nicotine-perfused striatum was significantly higher than that in control striatum. Preinjection of mecamylamine (3 mg/kg), a nicotinic antagonist, had no effect on either extracellular dopamine levels or on the BP of [(11)C]raclopride. These findings suggest that the high dose of local nicotine administration induced mecamylamine-insensitive local increases in extracellular dopamine, but might have decreased the total amount of extracellular dopamine in the striatum.