Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats

Abstract

The pituitary neuropeptide oxytocin promotes social behavior, and is a potential adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may mediate pro-social effects by modulating monoamine release in limbic and cortical areas, which was investigated herein using in vivo microdialysis, after establishing a dose that did not produce accompanying sedative or thermoregulatory effects that could concomitantly influence behavior. The effects of oxytocin (0.03-0.3 mg/kg subcutaneous) on locomotor activity, core body temperature, and social behavior (social interaction and ultrasonic vocalizations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V receptors. Dopamine and serotonin efflux in the prefrontal cortex and nucleus accumbens of conscious rats were assessed using microdialysis. 0.3 mg/kg oxytocin modestly reduced activity and caused hypothermia but only the latter was attenuated by the V receptor antagonist, SR49059 (1 mg/kg intraperitoneal). Oxytocin at 0.1 mg/kg, which did not alter activity and had little effect on temperature, significantly attenuated phencyclidine-induced hyperactivity and increased social interaction between unfamiliar rats without altering the number or pattern of ultrasonic vocalizations. In the same rats, oxytocin (0.1 mg/kg) selectively elevated dopamine overflow in the nucleus accumbens, but not prefrontal cortex, without influencing serotonin efflux. Systemic oxytocin administration attenuated phencyclidine-induced hyperactivity and increased pro-social behavior without decreasing core body temperature and selectively enhanced nucleus accumbens dopamine release, consistent with activation of mesocorticolimbic circuits regulating associative/reward behavior being involved. This highlights the therapeutic potential of oxytocin to treat social behavioral deficits seen in psychiatric disorders such as schizophrenia.

Blocking mu-opioid receptors inhibits social bonding in rituals

“…Although the sample size of study 1 is small, it adds significantly to study 2 by showing that the results hold across two different cultures and ritual types, thereby providing strong ecological validity [ 39 ]. Although it is possible that other neurochemicals such as oxytocin [ 45 , 46 ] and dopamine [ 47 ] might also play a role in the social bonding experience, studies of the receptor genetics for these other neurochemicals suggest that these play a more specialized and much less prominent role compared with β-endorphins [ 1 , 4 ]. Still, future research could seek to rule out the role of other such neurochemicals that have been proposed to play a role in bonding in further double-blind studies to determine which neurochemicals are necessary and/or sufficient for social bonding to occur.…”

The Role of Central Serotonin Neurons and 5-HT Heteroreceptor Complexes in the Pathophysiology of Depression: A Historical Perspective and Future Prospects

“…It is important to notice that the 5-HT2AR protomer upon its activation had a dominating role which resulted in a stronger attenuation of the OXTR-mediated Galphaq signaling (IP3 and intracellular calcium levels) than of 5-HT2AR mediated Galphaq signaling. The above results are of substantial interest since the dominating role of the 5-HT2AR protomer, a 5-HT receptor known to enhance depression, may do so in part by reducing OXTR protomer signaling, which improves social behaviors and mood, provided that this antagonistic allosteric cross-talk also exists in the brain OXTR heteroreceptor complexes [ 65 , 66 , 67 , 68 ]. It is also of interest that in co-transfected (5-HT2AR and OXTR) living cells, the 5-HT2AR antagonist blocking the 5-HT2AR protomer signaling could not restore the OXTR signaling in the receptor complex.…”

Victory is its own reward: oxytocin increases costly competitive behavior in schizophrenia

“…In humans, oxytocin administration has been shown modulate processing of social cues in the VTA (Groppe et al ., 2013), and neural responses to social reward correlate with plasma oxytocin levels (Strathearn et al ., 2009). Recent evidence also suggests that oxytocin system dysfunction may play a role in the pathophysiology of neuropsychiatric disorders that involve core social impairments, such as schizophrenia (Peñagarikano et al ., 2015; Kohli et al ., 2018) and autism (Gordon et al ., 2016), generating interest in oxytocin's potential as a treatment. Though oxytocin may ameliorate aspects of abnormal social behavior in schizophrenia (Burkner et al ., 2017), a lack of sensitive, objective measures designed to illuminate its mechanisms of action has limited our ability to determine whether oxytocin has clinical utility (Bradley and Woolley, 2017).…”