A strong positive association between depression and
alcoholism is evident in epidemiological studies. Curiously, the incidence of smoking (
nicotine intake) is also very high among depressed individuals. Because neuronal
nicotinic receptors have been implicated in mood regulation as well as in reinforcing effects of alcohol, it was of interest to determine whether inherent changes in these receptors may be manifested in an animal model that expresses both depressive-like characteristics and high alcohol intake. Thus, Fawn-Hooded (FH) rats along with their control ACI rats were used to measure the density of the high affinity
nicotinic receptor in discrete brain regions. Furthermore, the effects of acute and chronic
nicotine on depressive-like characteristics of FH rats were also evaluated. Measurements of [(3)H]
cytisine binding (selective for
alpha4beta2 nicotinic receptor subtype) revealed a reduction in these receptors only in the striatum of FH rats, a result very similar to that observed in selectively-bred alcohol-preferring (P) rats. Administration of
nicotine acutely (0.4 mg/kg, sc) resulted in a significant reduction of immobility in the forced swim test (FST) in FH rats only, implying an
antidepressant-like effect of
nicotine. Another group of FH rats were administered 0.4 mg/kg
nicotine (daily, sc) for 14 days and their behavior in the FST was evaluated 22-24 h after the last injection. In this case,
nicotine also had a significant
antidepressant-like effect in FH rats suggesting no tolerance to
nicotine had occurred. The effects of
nicotine on FST behavior are very similar to those observed in Flinders Sensitive Line rats, a putative animal model of depression. Together, these findings provide additional evidence for
antidepressant-like effects of
nicotine and strengthen the postulated association between striatal
nicotinic receptors and high alcohol intake. Thus,
nicotinic receptors could be suitable targets for the development of novel
pharmacotherapy for treatment of depression and possibly
alcoholism.