Effects of MK-801 Pretreatment on Methamphetamine Reward-Related Locomotor Behavior and Ultrasonic Vocalizations

Methamphetamine (METH) is a popular substance of abuse that is traditionally thought to produce rewarding effects primarily through the dopaminergic system. However, it has been shown that other neurotransmitter systems contribute to the behavioral effects of METH. For example, growing evidence suggests that N-Methyl-D-aspartate (NMDA) receptors may be involved in METH reward. This thesis investigated the role of these receptors in METH-induced reward in laboratory rats using locomotor behavior and ultrasonic vocalizations (USVs). Locomotor behavior has long been used to assess drugs of abuse and ultrasonic vocalizations represent a relatively new approach to measuring reward and aversion in rats. In a preliminary study, it was found that the NMDA receptor antagonist, MK-801, produced complex, dose-dependent effects on METH-induced locomotor behavior and USVs. Of particular interest, MK-801 at a low dose resulted in a facilitation of METH-induced USVs, but at higher doses attenuated METH-induced USVs. For this thesis we investigated three doses of MK-801 (0.03 mg/kg, 0.05 mg/kg and 0.10 mg/kg) with two doses of METH (0.3 mg/kg and 1.0 mg/kg) in adult male rats to replicate and extend the preliminary findings. The examination of the role of NMDA receptors occurred in two separate experiments. This thesis was unable to replicate the preliminary finding and instead found an attenuation of METH reward across doses of MK-801. The first found an attenuation of METH-induced USVs by the two higher doses of MK-801 and no effect on by the lower dose. Locomotor activity was increased by all three doses. Very similar effects were observed in the second experiment at the lower dose of METH. The results point toward potential therapeutic use of NMDA receptor blockers in psychomotor stimulant abuse and addiction.