The effects of acetaldehyde on nicotine-induced transmitter levels in young and adult brain areas.
The aim of the present study was to examine the effect of acetaldehyde administration on neurotransmitters in the presence of nicotine in brain areas associated with cognition and reward. We assayed these effects via microdialysis in conscious freely moving male Sprague-Dawley rats. It was reported that low doses of acetaldehyde enhance nicotine self-administration in young, but not in adult rats. Since nicotine enhances reward and learning, while acetaldehyde is reported to enhance reward but inhibit learning, acetaldehyde thus would be likely to stimulate reward without stimulating learning. We hoped that examining the effects of acetaldehyde (on nicotine-mediated neurotransmitter changes) would help to distinguish reward mechanisms less influenced by learning mechanisms. To avoid the aversive effect of acetaldehyde, we used a low dose of acetaldehyde (0.16 mg/kg) administered after nicotine (0.3mg/kg). We analyzed six brain regions: nucleus accumbens shell (NAccS), ventral tegmental area (VTA), ventral and dorsal hippocampus (VH and DH), and prefrontal and medial temporal cortex (PFC, MTC), assaying dopamine (DA), norepinephrine (NE) and serotonin (5-HT) and their metabolites in young and adult rats. The effect of acetaldehyde on nicotine-induced transmitter changes was different in young as compared to adult rat brain regions. In the NAccS of the young, DA was not affected while NE and 5-HT were increased. In the adult in this area DA and NE were decreased, while 5-HT was not altered. In other areas also in many cases, the effect of acetaldehyde in the young and in the adult was different. As an example, acetaldehyde administration increased NE in young and decreased NE in adult DH. We found stimulation of nicotine-induced changes by acetaldehyde in seven instances - six of these were observed in areas in young brain, NE in four areas (NAccS, DH, VH, and PFC), and 5-HT in two (NAccS and DH). Only one increase was noted in adult brain (DA in VTA). Inhibition of nicotine-induced changes by acetaldehyde was noticed in four young brain areas (DA in PFC and MTC, 5-HT in VTA, and VH) and in 13 adult brain areas (DA in NAccS, DH, VH, PFC, MTC, NE in NAccS, DH, PFC, MTC, and 5-HT in DH, VH, MTC, and PFC). Thus acetaldehyde was more stimulatory in young and more inhibitory in the adult brain areas tested, which could explain its stimulating nicotine reward only in young animals. That increases in NE were noted only in young, decreases in NE only in adult brain areas further suggest the role of NE in the age-dependent response. In general, six areas showed some increase and four showed decrease in the young versus one showing increase and thirteen showing decrease in the adult. Clearly the effects of acetaldehyde in young animals are different from those in adult animals. Because acetaldehyde did not induce elevated DA levels in the NAccS of the young, we believe that the higher reward in the young caused by acetaldehyde is not likely due to DA changes in the accumbens. The increase of NE and 5-HT in the brain areas of the young only raises the possibility that they may play an important role in reward in some cases when DA in the accumbens does not. Areas involved in cognitive mechanisms and a number of transmitters seem to play a role in reward stimulation.
Sershen
H
H
Nathan Kline Institute, Orangeburg, New York, NY 10962, USA. Sershen@nki.rfmh.org
Shearman
E
E
Fallon
S
S
Chakraborty
G
G
Smiley
J
J
Lajtha
A
A
D000079:Acetaldehyde / Q000494:pharmacology*; D000375:Aging; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D002404:Catheterization; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013702:Temporal Lobe / Q000187:drug effects / Q000254:growth & development; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000254:growth & development
D002491:Central Nervous System Agents; D018722:Nicotinic Agonists; D012701:Serotonin; D009538:Nicotine; D000079:Acetaldehyde; D004298:Dopamine; D009638:Norepinephrine