Oxytocin and Addiction: A Review

Kovaćs, Gábor L.; Sarnyai, Zoltán; Szabó, Gyula

doi:10.1016/s0306-4530(98)00064-x

Cited by 177 publications

(93 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The capacity of centrally administered OT to delay tolerance to the sedative and ataxic effects of ethanol (10,14) has been known since the late 1980s. The present study suggests that this effect of OT on the development of tolerance may reflect the antagonistic action of OT on acute ethanol-induced sedation and ataxia and its blockade of ethanol potentiation of GABA-gated current at δ-GABA A Rs.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

Bowen

Peters

Absalom

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Even moderate doses of alcohol cause considerable impairment of motor coordination, an effect that substantially involves potentiation of GABAergic activity at δ subunit-containing GABA A receptors (δ-GABA A Rs). Here, we demonstrate that oxytocin selectively attenuates ethanol-induced motor impairment and ethanol-induced increases in GABAergic activity at δ-GABA A Rs and that this effect does not involve the oxytocin receptor. Specifically, oxytocin (1 μg i.c.v.) given before ethanol (1.5 g/kg i.p.) attenuated the sedation and ataxia induced by ethanol in the open-field locomotor test, wire-hanging test, and righting-reflex test in male rats. Using twoelectrode voltage-clamp electrophysiology in Xenopus oocytes, oxytocin was found to completely block ethanol-enhanced activity at α4β1δ and α4β3δ recombinant GABA A Rs. Conversely, ethanol had no effect when applied to α4β1 or α4β3 cells, demonstrating the critical presence of the δ subunit in this effect. Oxytocin had no effect on the motor impairment or in vitro effects induced by the δ-selective GABA A R agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, which binds at a different site on δ-GABA A Rs than ethanol. Vasopressin, which is a nonapeptide with substantial structural similarity to oxytocin, did not alter ethanol effects at δ-GABA A Rs. This pattern of results confirms the specificity of the interaction between oxytocin and ethanol at δ-GABA A Rs. Finally, our in vitro constructs did not express any oxytocin receptors, meaning that the observed interactions occur directly at δ-GABA A Rs. The profound and direct interaction observed between oxytocin and ethanol at the behavioral and cellular level may have relevance for the development of novel therapeutics for alcohol intoxication and dependence.A receptors (δ-GABA A Rs) play a major role in regulating tonic inhibition in the central nervous system (CNS) (1). The δ-GABA A Rs also represent one of the major targets of ethanol in the CNS, particularly at relatively low ethanol concentrations, and mediate some of the rewarding and ataxic effects of ethanol (2-8). For instance, a genetic polymorphism that exaggerates the actions of ethanol at δ-GABA A Rs also potentiates ethanolinduced motor impairment (2). Further, knockdown of δ subunit expression in the medial shell of the nucleus accumbens reduces alcohol intake in rats (6). Finally, overstimulation and subsequent internalization of α4βδ extrasynaptic GABA A Rs after persistent stimulation by ethanol seem to underlie the development of rapid tolerance to the ataxic effects of ethanol (4).The neuropeptide oxytocin (OT) is well-known for its regulatory role in mammalian sociability and various other central and peripheral physiological processes (9). Early preclinical studies suggested that OT can prevent the development of tolerance to the sedative and ataxic effects of ethanol in rodents (10) and also modulate the severity of ethanol withdrawal (11). More recent studies show that OT reduces alcohol intake in rats (12) and reduces the severity of a...

show abstract

Section: Discussionmentioning

confidence: 99%

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

Bowen

Peters

Absalom

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Because pup suckling as a rewarding social stimulus is linked to the mesolimbic dopaminergic system, it could be hypothesized that oxytocin promotes affiliation by enhancing dopamine neurotransmission. Indirect evidence in support of this notion comes from studies reporting that oxytocin interferes with the mesolimbic dopamine system by blocking or suppressing many of the behavioral effects of cocaine (Kovács et al, 1998). For example, pretreating rats with oxytocin reduces hyperactivity and stereotypy triggered by acute injections of cocaine (Kovács et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Pup Suckling Is More Rewarding Than Cocaine: Evidence from Functional Magnetic Resonance Imaging and Three-Dimensional Computational Analysis

Ferris¹,

Kulkarni²,

Sullivan³

et al. 2005

J. Neurosci.

190

178

View full text Add to dashboard Cite

Nursing has reciprocal benefits for both mother and infant, helping to promote maternal behavior and bonding. To test the "rewarding" nature of nursing, functional magnetic resonance imaging was used to map brain activity in lactating dams exposed to their suckling pups versus cocaine. Suckling stimulation in lactating dams and cocaine exposure in virgin females activated the dopamine reward system. In contrast, lactating dams exposed to cocaine instead of pups showed a suppression of brain activity in the reward system. These data support the notion that pup stimulation is more reinforcing than cocaine, underscoring the importance of pup seeking over other rewarding stimuli during lactation.

show abstract

“…Es wird spekuliert, dass sich die Wirkung von Baclofen durch die Aktivierung von Oxytocinneuronen im PVN entfaltet [49,50].…”

Section: Oxytocin Im Einsatz Gegen Suchtmechanismenunclassified

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

2017

View full text Add to dashboard Cite

Oxytocin and the mechanisms of alcohol dependenceSummary One of the crucial purposes of treating alcohol-dependent patients is to enhance their ability to stay abstinent after detoxification therapy. Anxiety and stress vulnerability are the main factors provoking alcohol craving and relapse. In the first months of abstinence, alcohol-dependent patients frequently show sleep disturbances, irritability and depression, indicating chronic activation of stress pathways. In addition, the loss of confidence in interpersonal interactions results in social withdrawal and reduced willingness to participate in therapeutic programs. Current research shows that the peptide hormone oxytocin exerts substantial anxiolytic effects and facilitates prosocial behavior. Oxytocin can be safely ap-K

show abstract

Oxytocin and Addiction: A Review

Cited by 177 publications

References 47 publications

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

Pup Suckling Is More Rewarding Than Cocaine: Evidence from Functional Magnetic Resonance Imaging and Three-Dimensional Computational Analysis

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

Contact Info

Product

Resources

About

Oxytocin and Addiction: A Review

Cited by 177 publications

References 47 publications

Oxytocin prevents ethanol actions at δ subunit-containing GABA A receptors and attenuates ethanol-induced motor impairment in rats

Oxytocin prevents ethanol actions at δ subunit-containing GABA A receptors and attenuates ethanol-induced motor impairment in rats

Pup Suckling Is More Rewarding Than Cocaine: Evidence from Functional Magnetic Resonance Imaging and Three-Dimensional Computational Analysis

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

Contact Info

Product

Resources

About

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats