Neuroscience Institute, 880 Petit Science Center, Georgia State University, Atlanta, GA 30303, United States.
Neuroscience Institute, 880 Petit Science Center, Georgia State University, Atlanta, GA 30303, United States.
Physiol Behav. 2022 Aug 1;252:113828. doi: 10.1016/j.physbeh.2022.113828. Epub 2022 Apr 30.
A reduction in the rewarding properties of social interactions is frequently a key contributor to neuropsychiatric disorders. Although much remains to be learned about the neural mechanisms governing social reward, numerous studies have found that oxytocin can enhance the salience of rewarding social interactions. As a result, oxytocin has been suggested as a pharmacotherapy for disorders characterized by a dampening of social motivation. However, exogenous oxytocin does not cross the blood-brain barrier effectively, which has led to the investigation of alternative approaches to induce central oxytocin release, such as pharmaceuticals targeting melanocortins. Although oxytocin treatment is widely viewed to increase social reward, there is also recent evidence that high concentrations of oxytocin can decrease social reward. In the present study we tested the hypothesis that alpha-melanocyte-stimulating hormone (αMSH) influences the rewarding properties of social interactions by acting on oxytocin receptors. Male and female Syrian hamsters were given intracerebroventricular infusions of saline, αMSH, or a cocktail containing αMSH and an oxytocin receptor antagonist during social conditioning with a same-sex hamster and then tested for a conditioned place preference. αMSH decreased preference for the socially-paired chamber compared to saline treatment, and administration of the oxytocin antagonist concurrent with αMSH administration returned subjects' preference to control levels. Importantly, αMSH treatments did not affect any measures of body composition or the specific social behaviors displayed during conditioning. These data suggest that melanocortin-targeting drugs should be administered carefully to avoid the possibility of decreasing the rewarding properties of social interactions.
社交互动奖赏属性的降低通常是神经精神疾病的一个关键因素。尽管关于调节社交奖赏的神经机制还有很多需要了解，但许多研究发现，催产素可以增强有奖励的社交互动的显著性。因此，催产素被认为是治疗以社交动机减弱为特征的疾病的一种药物治疗方法。然而，外源性催产素不能有效地穿过血脑屏障，这导致了对诱导中枢催产素释放的替代方法的研究，例如针对黑色素皮质素的药物。尽管催产素治疗被广泛认为可以增加社交奖励，但最近也有证据表明，高浓度的催产素会降低社交奖励。在本研究中，我们测试了这样一个假设，即α-促黑素细胞激素（αMSH）通过作用于催产素受体来影响社交互动的奖赏属性。雄性和雌性叙利亚仓鼠在与同性仓鼠进行社交适应时，接受脑室内注射生理盐水、αMSH 或含有αMSH 和催产素受体拮抗剂的混合物，然后进行条件性位置偏好测试。与生理盐水处理相比，αMSH 降低了对社交配对室的偏好，而在αMSH 给药的同时给予催产素拮抗剂则使受测者的偏好恢复到对照水平。重要的是，αMSH 处理不会影响身体成分的任何测量值，也不会影响在适应过程中表现出的特定社交行为。这些数据表明，黑色素皮质素靶向药物的给药应该谨慎，以避免降低社交互动奖赏属性的可能性。
