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UBC Theses and Dissertations
Differential effects of the t-type calcium channel antagonist, Z944, on behaviours associated with amphetamine and morphine addiction Cunningham, Jonathan
Mixed L-/T-type calcium channel antagonists attenuate morphine- and amphetamine induced conditioned place preference (CPP). Subtype specific antagonists for T-type calcium channels attenuate nicotine-reinforced behaviours in rats. This thesis investigated the effects of a novel T-type calcium channel antagonist, Z944, on the acquisition, expression, and reinstatement of amphetamine and morphine CPP. Furthermore, we examined Z944 for aversive or rewarding properties, and determined changes in locomotion with Z944 alone and in conjunction with amphetamine or morphine. CPP was induced with either morphine (5.0 mg/kg, IP) or amphetamine (1.5 mg/kg, IP) and Z944 (vehicle, 5.0, 7.5 mg/kg, IP) was administered 15 min prior to conditioning sessions for CPP acquisition experiments. For CPP expression experiments, Z944 was administered prior to the test session. In a related experiment Z944 was administered 15 min prior to the reinstatement injection of morphine after a period of extinction. Aversive and rewarding properties of Z944 were evaluated using a CPP/CPA procedure. Z944 dose-dependently attenuated the acquisition of morphine CPP, the expression of amphetamine CPP, and drug-induced reinstatement of both amphetamine and morphine CPP. Further, Z944 alone had no inherent rewarding or aversive effects, despite causing a decrease in spontaneous locomotor activity. It was also revealed that Z944 attenuated amphetamine-induced hyperlocomotion and potentiated morphine-induced hypolocomotion. These results suggest that T-type calcium channel antagonists differentially attenuate behaviours induced by several classes of drugs of abuse.
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