Locally administered low nicotine-induced neurotransmitter changes in areas of cognitive function.
The present study examined the effect of a low-dose of nicotine; below that one expects to be achieved from a single cigarette, on brain regional heterogeneity and sensitivity of catecholaminergic responses. 1 microM nicotine was infused into six brain areas via a microdialysis probe: the dorsal and ventral hippocampus, the medial temporal and prefrontal cortex, the basolateral amygdala, and the ventral tegmental area (VTA). The nicotine concentration in the brain tissue near the probe site was approximately 0.1 microM. Nicotine-induced increases and decreases could be noted in dopamine (DA), norepinephrine (NE), and serotonin (5HT) levels. In particular, DA and 5HT decreased in both hippocampal areas, while NE increased in the dorsal and decreased in the ventral hippocampus. In the cortical areas, DA and NE increased and 5HT was not significantly altered. In the amygdala all three neurotransmitters increased and in the VTA, all three decreased. Many of the nicotine-induced changes in neurotransmitter concentrations were reversed in the presence of atropine. Where nicotine induced decreases in DA and 5HT in the VTA, increases were observed in the presence of atropine. A similar reversal was seen with NE in the VTA and ventral hippocampus. In contrast, the increases in DA observed in the cortex and amygdala and the increases in NE observed in the cortex, amygdala and dorsal hippocampus were inhibited by the presence of atropine. 5HT was also significantly decreased in the amygdala and both cortical areas in the presence of atropine, where nicotine alone had no significant effect. We conclude, that at low doses, nicotine significantly alters the release of DA, NE, and 5HT--in some areas increasing, in others decreasing endogenous neurotransmitter levels. This data, in conjunction with previous experiments, indicates that the effects of nicotine are regionally heterogeneous and arise from both direct and indirect actions on various receptors and neurotransmitter systems and nicotine's effects at low doses differ from that at higher doses. The changes in effects in the presence of atropine suggest that muscarinic acetylcholine receptors play a major role in nicotine's actions on neurotransmitter systems.
Shearman
E
E
Nathan Kline Institute, Orangeburg, New York 10962, USA.
Rossi
S
S
Sershen
H
H
Hashim
A
A
Lajtha
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition; D004305:Dose-Response Relationship, Drug; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018377:Neurotransmitter Agents; D009538:Nicotine; D001285:Atropine