The Effect of Lateral Septal GABAB Receptors on Morphine Sensitivity in Male Wistar Rats by Conditioned Place Preference

Behavioral sensitivity in response to morphine injection is a suitable model for studying the neuronal substrates of behavioral plasticity that is associated with reward and opioid abuse. The lateral septum (SL) plays a vital role in the reward and learning processes. The LS nucleus contains GABAergic neurons, and the outputs of this region into the ventral tegmentum (VTA) precisely regulate the amount of released dopamine. In the present study, we investigated the effects of injection of GABAB receptor agonists and antagonists on behavioral sensitivity to morphine in the conditioned place preference (CPP) model. In this experimental study, male Wistar rats were divided into 17 groups. Doses of 0.5, 1, 2.5, 5, 7.5, 10, 12.5, and 15 mg/kg of morphine were injected subcutaneously (S.C) into animals to determine effective and ineffective doses of morphine. An adequate amount of morphine was injected for 3 days to induce sensitization; after 5 days, CPP was performed with an ineffective dose of morphine. Doses of 1.5, 6, and 12 / µg/rat of agonist (baclofen) and antagonist (CGP35348) were injected into LS in the first 3 days of sensitization, 10 minutes before morphine injection. Baclofen at 6 µg/rat (p<0.05) and CGP35348 at 12 µg/rat (p<0.01) significantly reduced morphine sensitivity. GABAB receptors in the LS region can be an important target in the treatment of drug abuse.