B. Soderpalm et al., Nicotinic mechanisms involved in the dopamine activating and reinforcing properties of ethanol, BEH BRA RES, 113(1-2), 2000, pp. 85-96
Ethanol shares with all major dependence producing drugs the ability to act
ivate brain mesocorticolimbic dopamine neurons, an important part of the br
ain reward systems. This dopamine activation may be involved in mediating t
he positive reinforcing effects of ethanol. The mechanisms of action of eth
anol in its activation of this dopamine system remain, however, to be eluci
dated. A selective pharmacological interference with these mechanisms may o
ffer a possibility to reduce the reinforcing properties of ethanol without
simultaneously interfering with the reinforcing properties of natural rewar
ds. Ethanol has been shown to directly influence the function of various li
gand-gated ion-channels. Several of these are located on or nearby mesocort
icolimbic dopamine neurons. One such receptor is the nicotinic acetylcholin
e receptor (nAChR). The present article reviews a series of investigations
aimed at investigating whether nAChRs are involved in the dopamine activati
ng and reinforcing properties of ethanol. To this end acute and chronic beh
avioral acid neurochemical experiments were performed in mice and rats. The
results obtained indicate that central nAChRs in the ventral tegmental are
a are involved in mediating the mesolimbic dopamine activating and reinforc
ing effects of ethanol. Furthermore, the ethanol-induced activation of thes
e receptors is probably indirect, subsequent to a primary interference of e
thanol in the nucleus accumbens. Moreover, subchronic nicotine treatment en
hances the reinforcing and dopamine activating properties of ethanol. This
long-term effect may, however, derive from autonomic adaptations in respons
e to intermittent blockade of peripheral nAChRs (rather than from intermitt
ent stimulation of central receptors), and appears to be associated with de
velopment of a disinhibitory behavior that could involve also other neurotr
ansmittors, e.g. serotonin. Taken together, these findings could provide a
neurobiological explanation to the often observed co-abuse of nicotine and
ethanol in man. Furthermore, since the behavioral models applied previously
have predicted therapeutic drug effects in the clinic, the results suggest
that selective blockade of the ventral tegmental nAChRs that are involved
in the above effects may provide a new pharmacological alternative in the t
reatment of alcoholism. (C) 2000 Elsevier Science B.V. All rights reserved.