The Inhibitory Effect of VTA Cholinergic Receptors on Morphine State Dependent Memory in Rat

It is well known that morphine influence learning and memory processes. The ventral tegmental area (VTA) which involves in rewarding, also has an important role in morphine-induced impairment of memory retention. Knowing that the cholinergic system is involved in the effects of morphine on memory, in the present study, the effects of intra-VTA injections of muscarinic and nicotinic cholinergic receptor antagonists on morphine-induced memory has been investigated in rats.

A step-through passive avoidance task was used for the assessment of memory retention in male Wistar rats. Animals were bilaterally cannulated in the ventral tegmental area by stereotaxic instrument, and were recovered 1-week before behavioral testing.

Post-training subcutaneous (s.c.) administration of different doses of morphine dose dependently decreased the learning and induced amnesia. The administration of the same dose of morphine as pre-test treatment induced state-dependent learning. Pre-test intra-VTA administration of atropine (1, 2 and 3 µg/rat) alone could not affect memory retention; While, pretest intra-VTA injection of atropine 5 min before the administration of morphine (5 mg/kg) dose dependently inhibited morphine state-dependent learning. Pre-test intra-VTA microinjection of mecamylamine (1, 2 and 3 µg/rat) significantly decreased morphine state-dependent learning. Moreover, Pre-test intra-VTA administration of the higher dose of mecamylamine significantly decreased the step-through latencies, showing an amnestic effect.

The present findings indicate that the processes of learning in animals can be affected by morphine and the opioid produces state-dependent learning. Moreover, it can be concluded that inactivation of the muscarinic and nicotinic acethylcoline receptors in the VTA are involved in mediating morphine state-dependent learning.