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, 175, 133-139

Role of Cortical alpha-2 Adrenoceptors in Alcohol Withdrawal-Induced Depression and Tricyclic Antidepressants

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Role of Cortical alpha-2 Adrenoceptors in Alcohol Withdrawal-Induced Depression and Tricyclic Antidepressants

Bruk Getachew et al. Drug Alcohol Depend.

Abstract

Introduction: Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available.

Methods: In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3h daily for 10days (blood alcohol concentration ∼150mg%) followed by daily injection of 10mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand.

Results: Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains.

Conclusions: The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity.

Keywords: Alcohol use disorder; Alcohol withdrawal; Alpha-2 adrenoceptors; Animal model; Depression; Female Wistar-Kyoto (WKY) rats; Tricyclic antidepressants.

Conflict of interest statement

Conflict of interest statement

The authors have no conflict of interest to declare concerning the data presented in this report.

Figures

Figure 1
Figure 1
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on immobility scores in the forced swim test in female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8). **p <0.01 compared to control.
Figure 1
Figure 1
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on immobility scores in the forced swim test in female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8). **p <0.01 compared to control.
Figure 2
Figure 2
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on open field locomotor activity in female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8).
Figure 2
Figure 2
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on open field locomotor activity in female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8).
Figure 3
Figure 3
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on alpha-2 ARs density (fmole/mg Pr) in the frontal cortex of female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8). *p<0.05, **p <0.01 compared to control. +p<0.05 compared to alcohol group.
Figure 3
Figure 3
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on alpha-2 ARs density (fmole/mg Pr) in the frontal cortex of female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8). *p<0.05, **p <0.01 compared to control. +p<0.05 compared to alcohol group.
Figure 4
Figure 4
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on alpha-2 ARs density (fmole/mg Pr) in the hippocampus of female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8).
Figure 4
Figure 4
Effects of chronic alcohol, imipramine (IMP) and nomifensine (NOMI) on alpha-2 ARs density (fmole/mg Pr) in the hippocampus of female Wistar (A) and WKY (B) rats. Values are mean ± SEM (n=7–8).

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