Effect Of N-calcium Channel Antagonist ω-CTX MVIIA On The Development And Expression Of Conditioned Place Preference Induced By Morphine In Rat

1 ObjectiveTo study the effect of N-calcium channel antagonist ω -CTX MVIIA on the development and expression of conditioned place preference (CPP) induced by morphine in rat and meanwhile observe whether ω -CTX MVIIA itself would induce CPP and effect the locomotor activity.2 Materials and Methods2.1 AnimalsMale adult Sprague-Dawley rat.2.2 DrugsMorphine hydrochloride injection, Saline, GST-CTX MVIIA, CTX MVIIA.2.3 ApparatusSingle Manipulator Stereotaxic, The computer-based video-tracking CPP apparatus, RatTrack.2.4 Methods2.4.1 Effect of ω -CTX MVIIA on the development and expression of CPP induced by morphine: Male Sprague-Dawley rats were administered morphine (10mg/kg, sc) in white chamber for 50 min on d1, 3, 5, 7. On d2, 4, 6, 8 rats were given saline (1ml/kg, sc) in black chamber for 50 min. On d9 did the CPP test. Different doses of GST-CTX MVIIA(30,10,3 μ g/kg, icv) or CTX MVIIA (1,0.5, 0.25,0.125 μ g/kg, icv) were given (icv) 15 min before the administration of morphine to identify the effect of ω -CTX MVIIA on the development of CPP induced by morphine, and different doses of CTX MVIIA (2,1, 0.5 μ g/kg, icv) were given 15 min before the CPP test on d9 to identify the effect of ω -CTX MVIIA on the expression of CPP induced by morphine.2.4.2 Self preference of ω-CTX MVIIA: Six groups of male Sprague-Dawley rats were trained separately with GST-CTX MVIIA (30, 10, 3 μ g/kg, icv) or CTX MVIIA(0.5, 0.25, 0.125 μ g/kg, icv) in white chamber for 50 min on d1, 3, 5, 7; On d2, 4, 6, 8 all rats were given PBS (5ul, icv) in black chamber for 50 min, then on d9, they were tested whether to -CTX MVIIA could induce CPP.3 Results3.1 10mg/kg morphine (sc) induced rats obtaining a significant place preference, and did not affect the rats' locomotor activity and exploring activity;3.2 0.5 μ g/kg CTX MVIIA administered (icv) before morphine administration blocked the development of CPP induced by morphine, and did not affect the rats' locomotor activity and exploring activity;3.3 Three doses of CTX MVIIA did not blocked the expression of CPP induced by morphine, and partly reduce the rats' exploring activity;3.4 All doses of ω-CTX MVIIA did not induce CPP, and did not affect the rats' locomotor activity and exploring activity.4 Conclusionω -CTX MVIIA can intervene in reinforced effect induced by morphine at the doses that cannot induce CPP, and did not effect the rats' locomotor activity and exploring activity, which suggests that ω -CTX MVIIA might be useful in the treatment of opiate psychological dependence. It is hinted that N-VGCCs are involve in drug addiction and might be one of the mechanism of drug addiction. However the therapeutic window of ω -CTX MVIIA is small, not only as antalgic, but also as abstainer.