It is well established that exposure to drugs not only leads to the development of compulsive drug seeking/taking behaviors in humans as well as in animals but also causes a compulsive-like behaviors for natural rewards (sex, food, social et al) in abused drug users. Clinical research has found high rate of comorbidity between substance use disorder and eating disorders as well as compulsive sexual behaviorone. Moreover, substance use and compulsive-like behaviors show similar phenomenological features, such as craving, dependence, loss of control, and abstinence, perhaps they share a common possible pathophysiology.
One of our previous studies has demonstrated that morphine exposure-induced diminished consummatory and motivational behaviors for natural rewards (anhedonia-like behaviors) after acute or short-, but not long-term withdrawal(1-week), and developed motivational sensitization to natural rewards after protracted withdrawal period. More notably, the anhedonia-like behaviors coexisted with heightened craving for the high-incentive reward following short-term withdrawal, i.e., despite the consummatory and motivational anhedonia-like responses to multiple rewarding stimuli (less than 60% sucrose solution and sexual performance ), the PR responding for 60% sucrose solution and the risky appetitive behavior for sexual stimulus was markedly increased. And the appetitive motivational behaviors persist only when the morphine-treated rats are facing the high-value rewards (i.e., 60% sucrose and sexual reward). Thus we regard that morphine-induced maladaptive behavior at least partially differ from the reward incentive motivation. In fact, there is another component, i.e., the dysfunction of top-down inhibitory control caused by repeated drug use that may contribute to the high comorbidity rates of pathological pursuit of natural rewards in drug abusers. Several studies demonstrate that deficits in inhibitory control/executive control could be implicated in these disorders (eating disorder and compulsive sexual behavior).
Therefore, this study aimed to use a conflict task, which can reflect the ability of inhibitory control, to assess compulsive-like appetitive behaviors for natural rewards (i.e., 60% sucrose solution and a sexual partner) under punishment after short-term withdrawal from morphine. Then its probable neural mechanisms are discussed by behavior pharmacological methods based on the conflict model, in order to attain a better understanding of the neurobiological underpinnings of compulsive-like behaviors and also to aide in the development of new therapeutic interventions that could be effective in these disorders. And we found:
1. The results of experiment 1 and 2 showed that, compared to the saline-treated rats, the morphine-treated rats displayed a significantly higher performance for 60% sucrose solution under the foot-shock punishment. The sexually experienced male rats pretreated with morphine displayed more appetitive behaviors and the shorter latency to approach the sexual stimulus despite the foot shock as a punishment, which indicated that the morphine-treated rats displayed compulsive-like behaviors for nature rewards suggesting impairment in inhibitory control which may contribute to the comorbidities between drug abuse and other compulsive-like behaviors.
2. A multitude of studies had suggested that deficits in prefrontal cortical function (including ACC) and consequential impaired performance with inhibitory control could be crucial in promoting compulsive drug use, which is consistent with our study. In experiment 3, bilateral inactivation of ACC impaired the inhibitory control and induced compulsive-like behavior in saline-treated rats, while didn’t influence morphine-treated rats’ performance. On the contrary, morphine-treated induced impairment of inhibitory control was rescued by bilateral activation of ACC(experiment 4-5). The study further strengthened the evidence dysfunction in ACC played critical role in compulsive-like motivational behaviors.
3. As for saline-treated group, disconnection between ACC and BLA evoked compulsive-like behavior on Sal + Cont group, inactivation of ACC-CeA have no significant effect on it. For morphine-treated group, it seemed to make no different at all after disconnection of ACC and Amy. This suggested that BLA-ACC and ACC-CeA were responsible for different behavior regulation in Sal-treated group, and the role of the pathways between ACC and Amy need to be validated prospectively using activation methods owing to morphine pretreatment had destroyed some certain brain function including the ACC.