Effects of nicotine, methamphetamine and cocaine on extracellular levels of acetylcholine in the interpeduncular nucleus of rats.
There is increasing evidence that the cholinergic habenulo-interpeduncular pathway and the dopaminergic mesolimbic pathway may jointly mediate the reinforcing properties of addictive drugs. However, the effects of addictive drug on the functioning of the habenulo-interpeduncular pathway have not been well-characterized. Thus, several drugs of abuse (i.e., nicotine, cocaine, amphetamine) have been shown to alter the morphology of the habenulo-interpeduncular pathway, causing selective degeneration of the cholinergic neurons in this area. On the other hand, morphine was shown to alter the neurochemistry of the habenulo-interpeduncular pathway, inducing biphasic changes in acetylcholine release in the interpeduncular nucleus. In order to determine the effects of cocaine, amphetamine and nicotine on cholinergic neurotransmission in the habenulo-interpeduncular pathway, levels of acetylcholine were assessed during microdialysis in freely moving rats. Nicotine (0.1 and 0.4 mg/kg s.c.) produced a dose-dependent decrease in extracellular levels of acetylcholine, while methamphetamine (1 and 4 mg/kg i.p.) produced an increase in acetylcholine release in the interpeduncular nucleus. Cocaine (5 and 20 mg/kg i.p.) produced a biphasic effect on extracellular acetylcholine release, i.e., a low dose enhanced the release of acetylcholine and a high dose decreased its release. These results suggest that the habenulo-intepeduncular pathway may be a common target for drugs of abuse and, by modulating the mesolimbic pathway, may mediate unique aspects of the rewarding effects of different drugs.
Hussain
Rifat J
RJ
Center for Neuropharmacology and Neuroscience, MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, United States of America.
Taraschenko
Olga D
OD
Glick
Stanley D
SD
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D045604:Extracellular Fluid / Q000187:drug effects; D005260:Female; D008694:Methamphetamine / Q000494:pharmacology*; D017551:Microdialysis / Q000379:methods; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D008694:Methamphetamine; D009538:Nicotine; D003042:Cocaine; D000109:Acetylcholine