Antidepressant-like effects of nicotine and reduced nicotinic receptor binding in the Fawn-Hooded rat, an animal model of co-morbid depression and alcoholism.
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.
Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, United States. ytizabi@howard.edu
Yousef
Y
Tizabi
Bruk
B
Getachew
Amir H
AH
Rezvani
Sheketha R
SR
Hauser
David H
DH
Overstreet
D000437:Alcoholism / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000470:Alkaloids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001392:Azocines / Q000378:metabolism; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D011807:Quinolizines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013550:Swimming; D014316:Tritium / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D000928:Antidepressive Agents; D001392:Azocines; D009538:Nicotine; D011807:Quinolizines; D011978:Receptors, Nicotinic; D014316:Tritium; C004712:cytisine; D000093843:Quinolizidine Alkaloids