Galanin (1-15) and escitalopram combination in rats reduces alcohol consumption in the ethanol self-administration test and improves escitalopram effects in the forced swimming test.

Abstract

Recently, we described that Galanin(1-15)[GAL(1-15)] enhanced Escitalopram(ESC) effectiveness in depression symptoms. Moreover GAL(1-15) induces a substantial reduction in alcohol consumption. To investigate the effect of GAL(1-15) on ESC-activity in depression-alcoholism comorbidity, we used the ethanol self-administration test and the forced swimming test(FST) in rats, after a chronic alcohol consumption. Also to study if GAL(1-15)+ESC modulate the reward system induced by different reinforcers we have analyzed this combination in the saccharine self-administration test. Groups of rats received three times intraperitoneal injections of ESC (2.5mg/Kg or 7.5mg/Kg) 23, 5 and 1h before the test and one icv injection of GAL(1-15) (0.3nmol or 1 nmol) 15 minutes before the test. One-way ANOVA followed by Fisher´s least significant difference test was used. In the saccharin self-administration test, the coadministration GAL(1-15)(1nmol) and ESC(2.5mg/Kg) induced a strong reduction in the number of reinforcements of saccharine (p<0.05) and in number of active lever presses (p<0.05). In the ethanol Self-Administration test, GAL(1-15)(0.3nmol) enhanced the reduction of alcohol intake mediated by ESC(2.5mg/Kg). GAL(1-15) decreased the number of alcohol reinforcements (p<0.01) and the number of active levers pressed (p<0.01) by around 50% induced by ESC. In FST, in rats under a chronic alcohol consumption, GAL(1-15) reversed adverse ESC-mediated effects. The coadministration of GAL(1-15)(1nmol) and ESC(7.5mg/Kg) showed a significant decrease in immobility (p<0.05) and an increase in swimming(p<0.05) compared with ESC group. The results open up the possibility to use GAL(1-15) in combination with Escitalopram as a novel strategy in AUD comorbidity with depression.