The Effect of Desglycinamide‐(ARG⁸)‐Vasopressin (DGAVP) on the Acquisition of Free‐Choice Alcohol Drinking in Rhesus Monkeys

Abstract

The vasopressin analog desglycinamide-(Arg8)-vasopressin (DGAVP) has been reported to reduce the acquisition of heroin and cocaine self-injection behavior in rats. This led to the hypothesis that DGAVP can reduce the self-administration of psycho-active drugs (including ethanol) by attenuating central reinforcement processes. Under forced ingestion conditions, DGAVP has been reported, however, to enhance alcohol drinking in rats. We studied the effect of DGAVP on the acquisition of voluntary, free-choice alcohol drinking in naive rhesus monkeys, that had concurrent access to either 1% and 2% (n = 12) or to 4% and 8% (n = 8) ethanol/water solutions in addition to drinking water. Half of the monkeys were injected twice per day with 50 micrograms.kg-1 of DGAVP for 14 successive days, the other half received placebo. Subsequently, all subjects had access to the same solutions for another 14 days without treatment. DGAVP did not significantly affect concentration preference behavior. With regard to net ethanol ingestion in animals drinking 1% and 2% solutions, DGAVP decreased net ethanol intakes, having a time-dependent and long lasting effect; placebo-treated animals gradually increased net ethanol intakes over time. The placebo-treated animals in the 4% and 8% group, showed a different acquisition pattern; DGAVP reduced net ethanol intake in two animals in a similar way as above. Two animals behaved differently. It is concluded that in a free-choice condition DGAVP did not enhance the acquisition of alcohol drinking in monkeys, but rather inhibited ethanol self-administration in the majority of the subjects.

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

“…Of interest, the AVP fragment DGAVP, which lacks the classical endocrine actions of vasopressin and is only centrally active (de Wied et al, 1972), was found to inhibit alcohol self-administration in monkeys (Kornet et al, 1991) and reduce alcohol intake in Brattleboro homozygote rats (Righter and Crabbe, 1985). This AVP analog was also reported to reduce the acquisition of heroinand of cocaine intravenous self-administration in rats (Van Ree et al, 1999).…”

“…It was found that removal of endogenous AVP by injecting AVP antiserum directly into the cerebrospinal fluid led to facilitation of heroin self-administration behavior, suggesting that AVP may be physiologically involved in central reinforcement processes (Van Ree and de Wied, 1977). Of interest, the AVP fragment DGAVP, which lacks the classical endocrine actions of vasopressin and is only centrally active (de Wied et al, 1972), was found to inhibit alcohol selfadministration in monkeys (Kornet et al, 1991) and reduce alcohol intake in Brattleboro homozygote rats (Rigter and Crabbe, 1985). This AVP analog was also reported to reduce the acquisition of heroin and of cocaine intravenous selfadministration in rats (Van Ree et al, 1999).…”

“…S INCE THE 1980s, evidence has emerged implicating arginine vasopressin (AVP) in the control of alcohol drinking. In fact, systemic administration of desglycinamide-(Arg 8 )-vasopressin (DGAVP, a centrally effective AVP fragment; de Wied et al, 1972) decreased alcohol intake in rhesus monkeys (Kornet et al, 1991). In studies exploring the role of AVP in Brattleboro homozygote rats lacking vasopressin, DGAVP reduced alcohol intake (Rigter and Crabbe, 1985).…”

Vasopressin and alcohol: a multifaceted relationship

“…But perhaps, most importantly, a recent clinical trial demonstrated a significantly greater percentage of days abstinent following V1b receptor antagonism for individuals who met the criteria for DSM-IV alcohol dependence (Ryan et al 2017). Conversely, 14 weeks of alcohol exposure with concurrent systemic DGAVP administration, the VP fragment that has reduced peripheral endocrinological activity compared to full VP, caused long lasting decreases in alcohol drinking in rhesus monkeys (Kornet et al 1991; Kornet et al 1992). One important difference between the Kornet et al (1991; 1992) studies and the other studies was that while the other studies initiated alcohol exposure followed by testing of the antagonist, this study did concurrent DGAVP administration with initial alcohol exposure.…”

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

“…In the 1980's to 1990's, evidence emerged implicating AVP in the motivational properties of alcohol, heroin and cocaine (see Van Ree et al, 1999). Systemic administration of the AVP fragment desglycinamide-(Arg 8 )-vasopressin was found to decrease alcohol intake in rhesus monkeys (Kornet et al, 1991). In studies exploring the role of AVP in Brattleboro homozygote rats lacking vasopressin, desglycinamide-(Arg 8 )-vasopressin reduces alcohol intake (Rigter and Crabbe, 1985).…”