Mediodorsal thalamic cannabinoid CB۱ receptors mediate the effect of exercise and enriched environment on dextromethorphan-induced anxiety in rats

Dextromethorphan (DXM), as a medication used to treat coughing, is an NMDA receptor antagonist that could be abused to induce rewarding effects in the brain. Evidence suggests that exercise may reduce the symptoms of anxiety. Thus, the aim of the present study was to investigate the possible effect of exercise and also enriched environment (EEN) on the DXM-induced anxiety, using the elevated plus-maze (EPM) test in male Wistar rats. The animals were divided to two groups: the exercise/EEN groups and normal groups. The exercise/EEN-juvenile rats (۵۰-۷۰ gr) were placed on treadmill and exposed to EEN about ۳۰ minute on a day for ۵ weeks(the protocol for using the treadmill was as follows: the first three weeks ۱۵ min, the fourth week ۲۰ min and the fifth week ۳۰ min), and then, they were bilaterally cannulated in the mediodorsal nucleus of thalamus (MD), using a stereotaxic surgical procedure. After recovering period, the anxiety-like behaviors were measured under the dugs’ administrations in the elevated plus-maze (EPM) test. Intraperitoneal administration of the different doses of DXM (۳-۷ mg/kg, i.p.) induced the anxiogenic-like behaviors in the EPM through decreasing the percentage of open arm time (%OAT) and open arm entries (%OAE). Interestingly, the anxiogenic effect of DXM was not observed in the exercise/EEN-rats, suggesting an improving effect of exercise and EEN rehabilitation on the anxiety. Furthermore, we found that microinjection of ACPA, as an agonist of CB۱ receptors into the MD, ۵ min before the administration of DXM (۷ mg/kg) potentiated the improving effect of exercise and EEN on the animals. Taken together, it can be suggested that the exercise and EEN can inhibit the anxiogenic effect of DXM which can be considered in clinical studies. In addition, the MD cannabinoid CB۱ receptors may be involved in the anxiolytic effect of rehabilitation on DXM administration.

کلیدواژه ها:

NMDA receptor antagonist ، Treadmill ، Elevated plus maze ، Rats