Adolescent Oxytocin Exposure Causes Persistent Reductions in Anxiety and Alcohol Consumption and Enhances Sociability in Rats

Abstract

Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33–42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A “booster” shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

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

“…It is through overstimulation and subsequent internalization of these receptors that rapid tolerance to ethanol's effects seems to develop (4). It is also possible that the effects described here are relevant to the inhibitory action of OT on ethanol consumption (12,19). A regionally specific knockdown of δ subunits in the medial shell of the nucleus accumbens reduces ethanol consumption in rats (6), whereas δ knockout mice are known to consume less ethanol than wild types (5).…”

“…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 alcohol withdrawal and craving in dependent humans during detoxification (13). However, the mechanism underlying these actions is largely uncharacterized, including whether the modulation of various alcohol-related effects by OT involves the OT receptor (OTR).…”

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…Finally, oxytocin systems play a role in various appetitive social behaviors, including pair bonding, mother-infant bonding, and social approach and recognition (Insel, 1992;Young et al, 2001;McGregor et al, 2008;Young et al, 2011). Male rats given oxytocin during early adolescence later exhibit enhanced social behavior, less anxiety-like behavior, and upregulated levels of oxytocin and oxytocin mRNA (Bowen et al, 2011). After oxytocin administration in adulthood, they also exhibit less alcohol drinking (Bowen et al, 2011), suggesting that upregulation of oxytocin may have a protective effect against alcohol intake (Bowen et al, 2011).…”

“…Male rats given oxytocin during early adolescence later exhibit enhanced social behavior, less anxiety-like behavior, and upregulated levels of oxytocin and oxytocin mRNA (Bowen et al, 2011). After oxytocin administration in adulthood, they also exhibit less alcohol drinking (Bowen et al, 2011), suggesting that upregulation of oxytocin may have a protective effect against alcohol intake (Bowen et al, 2011). Such systems are prime candidates for investigating the neural basis of social context at the time of drug initiation and on vulnerability to development of further drug use and dependence.…”

Psycho-Behavioral Spiral of Disturbances in Prosocial Behavior, Stress Response, and Self-Regulation inSubstance-Related and Addictive Disorders

“…Oxytocin reduces methamphetamine selfadministration, reinstatement of methamphetamine-seeking behavior, and methamphetamine-induced hyperactivity in rats [115]. Furthermore, oxytocin-treated rats show a reduction of anxiety-like behaviors and in alcohol consumption, and enhancement of social interaction as compared to controls [116]. Given these responses in laboratory animals, it is possible that oxytocin may be of value in treating similar symptoms in SRAD patients.…”