Effect of sub-effective dose of GABA agonists on attenuation of morphine tolerance in rats: Behavioral and electrophysiological studies

Abstract

GABAergic drugs can change analgesic effect of morphine. Wide dynamic range (WDR) neurons play an important role in pain transmission and may change behaviors in morphine tolerance. In this study WDR neuron behaviors in morphine tolerant rats and rats treated with GABA agonists, were recorded to elucidate the effect of morphine and GABA agonists on WDR behavioral changes. Rats were divided to 4 groups: 1. Control, 2. Morphine tolerance (MT), 3. MT+ muscimol, 4- MT+ baclofen. To induce morphine tolerance in rats, they received morphine sulfate 10 mg/kg intraperitoneally for 8 days. In treatment group, GABA agonists were injected on days 1, 3, 5 and 8 before injection of morphine. To confirm morphine tolerance induced, formalin test was used. Extracellular single unit recording was used to record spinal WDR neurons. Results showed that chronic administration of morphine failed to attenuate formalin pain but GABA agonists improved analgesic effect of morphine.