Nicotinic receptor-mediated regulation of the dopamine transporter in rat prefrontocortical slices following chronic in vivo administration of nicotine

• Published in: Schizophrenia research Vol. 65; no. 1; pp. 47 - 55
• Main Authors: Drew, Allison E., Werling, Linda L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2003; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Alkaloids; Amphetamine - pharmacology; Animals; Benzophenanthridines; Biological and medical sciences; Chronic nicotine treatment; Culture Techniques; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins; Dopamine release; Dopamine transporter; Injections, Subcutaneous; Male; Medical sciences; Membrane Glycoproteins; Membrane Transport Proteins - metabolism; Nerve Tissue Proteins; Nicotine; Nicotine - pharmacology; Phenanthridines - pharmacology; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Schizophrenia; Signal Transduction - drug effects; Signal Transduction - physiology; Stimulation, Chemical; Synaptosomes - drug effects; Synaptosomes - physiology; Tobacco Use Disorder - physiopathology; Tobacco, tobacco smoking; Toxicology; Schizophrenia; Dopamine transporter; Dopamine release; Chronic nicotine treatment; Nicotine; Rat; Central nervous system; Male; Cognition; Encephalon; Psychosis; Cholinergic receptor; Subcutaneous administration; Nicotinic receptor; Consumption; Dopamine; Rodentia; Prefrontal cortex; Catecholamine; Psychological effect; Experimental study; In vivo; Chronic; Vertebrata; Tobacco; Mammalia; Treatment; Animal; Dopamine agonist; Application method; Comparative study
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/S0920-9964(02)00500-5

Low levels of dopaminergic activity in prefrontal cortex are thought to contribute to negative symptoms of schizophrenia. Negative symptoms are associated with the prefrontocortical area of the brain. Schizophrenic patients have a high rate of smoking, which by subjective as well as objective measures produces a cognitive benefit. We have previously shown that agonists at nicotinic receptors containing α4 and β2 subunits can enhance amphetamine-stimulated [ 3H]dopamine ([ 3H]DA) release via the dopamine transporter (DAT) from slices of rat prefrontal cortex. This effect is selective for prefrontal cortex; the enhancement does not occur in striatum or nucleus accumbens. The enhancement is dependent upon activation of protein kinase C (PKC). In the current study, we show that the enhancement of amphetamine-stimulated [ 3H]DA release is maintained after 10 days of chronic nicotine treatment, delivered subcutaneously twice daily. There are no significant changes in the ability of prefrontocortical brain slices to take up [ 3H]DA in tissue prepared from nicotine-treated vs. saline-treated rats. Nicotinic receptors mediating enhancement of amphetamine-stimulated [ 3H]DA release are at least partially localized to nerve terminals, as an enhancement in release is also observed in synaptosomal preparations. Finally, the sensitivity of the nicotine enhancement in release to the PKC inhibitor chelerythrine is also seen in synaptosomal preparations, suggesting that the signaling mechanism activated through α4β2 receptors is intact.