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.
Highlights
The neuropeptide oxytocin (OT) regulates a number of critical behavioral repertoires in mammals including maternal behaviour [1,2,3], social interaction and social preference [4,5], sexual behaviour [6], and anxiety-like behaviour [2]
The anxiolytic and prosocial effects of OT evident in these animal models have led to worldwide interest in exogenous OT as a potential therapeutic for human psychiatric disorders [2,16,17,18,19,20,21,22,23]
The rats were at PND 33 at the start of dosing, an age corresponding to early adolescence
Summary
The neuropeptide oxytocin (OT) regulates a number of critical behavioral repertoires in mammals including maternal behaviour [1,2,3], social interaction and social preference [4,5], sexual behaviour [6], and anxiety-like behaviour [2]. The anxiolytic properties of OT, and related OT receptor agonists, have been documented in many different rodent models of anxiety and with many different routes of administration [7,8,9,10,11]. Social interaction deficits in prenatally stressed rat pups were reversed by administering OT into the central amygdala [12]. Central administration of OT reduced distress ultrasonic vocalisation production in rat pups during social isolation, perhaps by mimicking the effects of social contact [13]. Chronic central OT administration in male rats increased the duration and frequency of non-sexual physical contact with female rats, irrespective of their oestrous cycle, which suggests chronic OT may facilitate nonsexual social interactions [15]. The anxiolytic and prosocial effects of OT evident in these animal models have led to worldwide interest in exogenous OT as a potential therapeutic for human psychiatric disorders [2,16,17,18,19,20,21,22,23]
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