The effect of GABAB receptors in CA1 region of hippocampus on morphine tolerance in female Wistar race rats by conditioned place preference

The hippocampus is a region of the brain that plays an important role in learning activities, including conditioned place preference (CPP). This area is widely used as the target of the studies on the reinforcing effects of the drugs and narcotics. Considering the wide distribution of GABAB receptors in the hippocampus CA1 region, these receptors are likely to play an important role in drug reward learning.

Wistar female rats were divided into 17 groups (N=7). Different amounts of morphine (0.5, 2.5, 5, 7.5, and 10 mg/kg) were injected subcutaneously to determine the effective dose of morphine. 3 days before induction of conditioned place preference, the animals received morphine injection (12.5 mg/kg) in order to induce tolerance. Then, baclofen as a stimulant (agonist) of GABAB receptors; and also, CGP35348 as an inhibitor of these receptors (antagonists) were injected into the CA1 region of the hippocampus.

5 mg/kg of morphine was considered as the effective dose at the significance level of P< 0.001. Baclofen at the doses of 6 mg/kg and 1/5 mg/kg increased tolerance to morphine (P <0.01 and P <0.05 respectively). CGP35348 at a dose of 6 mg/kg significantly reduced morphine tolerance (P <0.05).

The results of this study confirmed the importance of GABAB receptors in the CA1 region of the hippocampus in morphine tolerance in female rats.