Involvement of Arginine Vasopressin and V1b Receptor in Alcohol Drinking in Sardinian Alcohol-Preferring Rats

Abstract

Background Recent animal studies have shown that the level of stress-responsive arginine vasopressin (AVP) gene expression in the amygdala is increased during early withdrawal from long-term heroin or cocaine administration. The selective AVP V1b receptor antagonist SSR149415 (capable of exerting antidepressant-like and anxiolytic effects in animal models) also blocked stress-induced reinstatement of drug-seeking behavior. The present study was undertaken to investigate the effects of alcohol and to determine whether: (1) there are genetically determined differences in basal AVP mRNA levels in the medial/central amygdala (Me/CeA) and medial hypothalamus (MH) between selectively bred Sardinian alcohol-preferring (sP) and -nonpreferring (sNP) rats; (2) the AVP mRNA levels are altered by long-term alcohol drinking in sP rats; and (3) the V1b receptor antagonist SSR149415 alters alcohol drinking in sP rats. Methods In Experiment 1, AVP mRNA levels were measured in the Me/CeA and MH of alcohol-naive sP and sNP rats, and sP rats exposed to the the standard, homecage 2-bottle “alcohol vs water” choice regimen 24 hours/day for 17 days. In Experiment 2, SSR149415 (0, 3, 10, or 30 mg/kg; i.p.) was acutely administered 30 min before lights off to alcohol-experienced sP rats. Alcohol, water, and food intake were monitored 6 and 24 hours later. Results We found higher basal AVP mRNA levels in both Me/CeA and MH of alcohol-naive sP than sNP rats; alcohol consumption decreased AVP mRNA levels in both brain regions of sP rats, suggesting genetically determined differences between the two rat lines and in the effects of alcohol drinking in sP rats. Acute treatment with SSR149415 significantly reduced alcohol intake of sP rats. Conclusion The stress-responsive AVP/V1b receptor system is one component of the neural circuitry underlying high alcohol drinking in sP rats.

Alcohol: A stimulant activating brain stress responsive systems with persistent neuroadaptation

“…Our recent studies on selectively bred Sardinian alcohol-preferring vs. Sardinian alcohol-nonpreferring rats showed similar results as reported above: [a] Sardinian alcohol-preferring rats display higher basal AVP mRNA levels in the paraventricular nucleus and medial amygdala than Sardinian alcohol-nonpreferring rats; and [b] voluntary alcohol consumption decreased the AVP mRNA levels in both the paraventricular nucleus and medial amygdala of Sardinian alcohol-preferring rats (Zhou et al, 2011a).…”

“…Our laboratory has further demonstrated that the V1b antagonist SSR149415, but not V1a antagonist, blocks stress-induced heroin seeking behavior, and blunts HPA activation by foot-shock or drug withdrawal stress (Zhou et al, 2008(Zhou et al, , 2011b. In our recent alcohol study, we have found that SSR149415 attenuates alcohol consumption in Sardinian alcohol-preferring rats, indicating that AVP is involved in modulating alcohol drinking behaviors through a V1b receptor-mediated mechanism (Zhou et al, 2011a). It has been further demonstrated that SSR149415 dose-dependently reduced excessive levels of alcohol self-administration in alcoholdependent Wister rats (induced by chronic intermittent alcohol vapor exposure), without affecting the limited levels of alcohol drinking in non-dependent rats (Edwards et al, 2012).…”

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

“…As the high degree of anxiety-like and depression-like states is partially attenuated after voluntary alcohol drinking, rodents may drink alcohol to improve their emotional states (negative reinforcing mechanism) [Colombo et al, 2006;Bell et al, 2012;Pang et al, 2013]. In our alcohol study with sP rats, V1b antagonist SSR149415 dose-dependently attenuates alcohol intake, suggesting that V1b receptor-mediated mechanism is involved in modulating alcohol drinking behaviors [Zhou et al, 2011a]. Importantly, SSR149415 reduces excessive alcohol self-administration in alcohol-dependent Wistar rats in a dose-dependent manner, without altering alcohol drinking in non-dependent rats [Edwards et al, 2012] (Table 1).…”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…In Sardinian rats, basal AVP mRNA levels in the MeA, CeA, and medial hypothalamus of alcohol-naive alcoholpreferring rats are higher than those in alcohol-nonpreferring rats, and alcohol consumption decreases AVP mRNA levels in these brain regions of alcohol-preferring rats (553). Acute treatment with the V1b receptor antagonist SSR149415 significantly reduced the alcohol intake of alcohol-preferring rats.…”