Acute and chronic nicotinic interactions with dopamine systems and working memory performance.
Nicotine has been found to improve memory performance in a variety of tests in rats, monkeys, and humans. Interactions of nicotinic systems with dopamine (DA) systems may be important for this effect. We conducted a series of studies of nicotinic agonist and antagonist interactions with DA systems using rats in a win-shift working memory task in the radial-arm maze. The working memory deficit caused by the nicotinic antagonist mecamylamine was potentiated by the D1/D2 DA antagonist haloperidol and the specific D2 antagonist raclopride. In contrast, the mecamylamine-induced deficit was reversed by co-administration of the D2/D3 agonist quinpirole. Nicotine also has significant interactions with dopamine drugs with regard to working memory performance in the radial-arm maze. The DA agonist pergolide did not by itself improve radial-arm maze memory performance, but when given together with nicotine it produced an elevated dose-dependent increase in choice accuracy. The D1 agonist SKF 38393 significantly impaired radial-arm maze choice accuracy. Nicotine was effective in reversing this deficit. When given together with nicotine, the D2/D3 agonist quinpirole improved RAM choice accuracy relative to either drug alone. Acute local infusion of mecamylamine to the midbrain DA nuclei effectively impairs working memory function in the radial-arm maze. In contrast to acute nicotinic manipulations, considerably less evidence exists that the effects of chronic nicotine administration are influenced by DA systems. This may be an example of the different neural substrates that underlie the memory improvement caused by acute and chronic nicotine.
Levin
E D
ED
Department of Psychiatry, Duke University Medical Center Research Service, Durham, North Carolina 27710, USA.
Rose
J E
JE
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004334:Drug Administration Schedule; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008464:Mecamylamine / Q000494:pharmacology*; D008568:Memory / Q000502:physiology*; D009538:Nicotine / Q000008:administration & dosage*; D011978:Receptors, Nicotinic / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology; D017557:Ventral Tegmental Area / Q000502:physiology
D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D004298:Dopamine