effects of clavulanic acid on the acquisition and reinstatement following morphine-induced conditioned place preference in mice

Introduction: β-lactam antibiotics like clavulanic acid (ca) enhances cellular glutamate uptake through activation of glutamate transporter subtype 1 (glt-1) and decreases the level of glutamate in the nervous system. based on studies, blocking the glutamate activity inhibits morphine-induced conditioned place preference (cpp) in animals. therefore, the effects of ca on the acquisition of morphine craving were evaluated using the cpp model in the current study. methods: ca (1, 50 and 150 mg/kg, ip) was co-administered with morphine (40 mg/kg) for 4 days in the conditioning phase. on day 8, the effects of ca on morphine preference was assessed. in another experiment, the effect of ca on reinstatement of morphine preference by a single morphine injection (10 mg/kg) was evaluated after an extinction period. results: in the first method, the morphine-induced place preference was markedly reduced following administration of ca (50 and 150 mg/kg). in the second experiment, a single administration of ca (50 and 150 mg/kg) markedly inhibited the reinstatement of morphine preference on day 16. the results indicated that ca (50, 150 mg/kg) can block both morphineinduced cpp and the reinstatement of place preference following priming dose of morphine. also memantine (as a positive control) (10 mg/kg) significantly inhibited both acquisition and reinstatement of morphine cpp. conclusion: considering the important role of glutamate neurotransmission in morphine dependence, the effects of ca may be partly due to decrease in glutamate level in synaptic space and blockade of n-methyl-d-aspartate acid (nmda) receptors. although, we need further studies to determine exact cellular mechanism.