Potentiation of rewarding properties of morphine by concurrent chemical stimulation of lateral hypothalamus in rats

Orexinergic projections from the lateral hypothalamus (LH) have an important role in acquisition of morphine conditioned place preference (CPP). However, little is known about the functional interaction between orexinergic and opioidergic systems in the reward circuitry in the rats. In the present study, we investigated the effects of different doses of carbachol, for chemical stimulation of LH, on rewarding properties of morphine in the rats. 132 adult male albino Wistar rats weighing 220-320 g were unilaterally implanted by a cannula into the LH. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. In this paradigm, we used different doses of carbachol (31.25, 62.5, 125 and 250 nmol/0.5 μl saline), as a cholinergic agonist, in the LH. In the next set of experiment, we concurrently administered the ineffective doses of carbachol (31.25 and 62.5 nmol) and morphine (1 mg/kg; a dose that produced no appreciable effect when given alone) during 3-day conditioning (Acquisition) and post-conditioning (Expression) phases. Our results showed that unilateral intra-LH administration of both ineffective doses of carbachol during conditioning phase significantly (P < 0.01) potentiated the development of CPP by morphine (1 mg/kg). However, in the expression experiments, only dose of 62.5 nmol/rat carbachol could induce morphine-CPP (P < 0.05). Our findings suggest that a chemical stimulation of LH in sub-threshold condition could potentiate rewarding properties of morphine through mechanisms involved in alteration of dopamine release or morphine sensitization at the level of nucleus accumbens and/or ventral tegmental area by orexin receptors in the rats.