Effects of Combinations of Methamphetamine and Dissociatives on Reward-Related Ultrasonic Vocalizations in Rats

Polydrug abuse, the use of two or more drugs in combination, is common among drugs users and addicts. One of the leading thoughts about drug combinations is that they are used because the combination produces rewarding effects that are greater than either drug alone. Drug users are more likely to combine drugs in settings where the abuse of these drugs overlap. For example, in the dance and rave scene, amphetamine-derived stimulants such as methamphetamine (METH) and dissociatives such as ketamine and PCP are regularly abused. Because of the similar setting in which METH and the dissociatives are abused, there is a higher probability for these drugs to be used simultaneously. The current thesis examined the rewarding effects of these drug combinations using ultrasonic vocalizations emitted by laboratory rats as a measure of drug reward. Ultrasonic vocalizations represent a relatively new approach to measuring affective (mood) state, reward and aversion. METH was examined in combination with the dissociatives ketamine, phencyclidine (PCP) and dizocilpine (MK-801). In two preliminary studies, it was found that ketamine paradoxically blocks the rewarding effects of METH and METH-induced locomotor activity. Because of these findings it was subsequently hypothesized that combining METH with PCP or MK-801 would decrease METH-induced reward as measured by ultrasonic vocalizations and locomotor activity. In addition, it was hypothesized that MK-801 and PCP would produce aversive effects as measured by ultrasonic vocalizations. It was found that PCP and MK-801 blocked METH-induced USVs, but increased locomotor activity induced by METH. In addition, MK-801 produced mild aversive effects, but PCP did not. The findings reveal a blockade of METH reward by dissociatives, and suggest that ketamine and related drugs may be useful in the treatment of METH abuse and addiction.