Oxytocin improves probabilistic reversal learning but not effortful motivation in Brown Norway rats. (15th May 2019)

• Record Type: Journal Article
• Authors: Roberts, Benjamin Z.; Young, Jared W.; He, Yinong V.; Cope, Zackary A.; Shilling, Paul D.; Feifel, David
• Is Part Of: Neuropharmacology. Volume 150(2019)
• Page Start: 15
• Page End: 26
• Publication Date: 2019-05-15
• Subjects: Oxytocin -- Reward learning -- Motivation -- Probabilistic learning -- Progressive ratio; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.02.028
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Deficits in cognition and motivation are common and debilitating aspects of psychiatric disorders, yet still go largely untreated. The neuropeptide oxytocin (OT) is a potential novel therapeutic for deficits in social cognition and motivation in psychiatric patients. However, the effects of OT on clinically relevant domains of non-social cognition and motivation remain under studied. The present study investigated the effects of acute and chronic (21-day) administration of subcutaneous OT (0.04, 0.2, and 1 mg/kg) in cross-species translatable operant paradigms of reward learning and effortful motivation in male and female Brown Norway (BN) rats (n = 8–10/group). Reward learning was assessed using the probabilistic reversal learning task (PRLT) and effortful motivation was measured using the progressive ratio breakpoint task (PRBT). As predicted, BN rats exhibited baseline deficits in the detection of reversals of reward contingency in the PRLT relative to Long Evans (LE) rats. The two strains performed equally in the PRBT. Thirty minutes after a single OT injection (1 mg/kg), measures of both initial probabilistic learning (trials to first criterion) and subsequent reversal learning (contingency switches) were significantly improved to levels comparable with LE rats. The OT effect on switches persisted in male, but not female, BN rats 30 min, 24 h, and 6 days after long-term OT administration, suggesting the induction of neuroplastic changes. OT did not affect effortful motivation at any time-point. The beneficial effects of OT on reward learning in the absence of increased effortful motivation support the development of OT as a novel therapeutic to improve cognitive functioning. Graphical abstract: Image 1 Highlights: Rats received daily OT for 21 days and tested in a reward learning task (PRLT). Rats also assessed in a effortful motivation task (PRBT). OT improved PRLT performance in males throughout testing. Only acute OT improved PRLT in females. Neither acute nor chronic OT had any significant effect on PRBT.