Involvement of Endogenous Opioids in Methamphetamine Reward

The rewarding effects of drugs contribute to drug abuse and the mechanisms behind drug reward involve multiple neurotransmitters. It is thought that amphetamines and related drugs produce reward by facilitating dopamine release in specific brain circuits whereas other research suggests that endogenous opioids are involved in amphetamine reward. An important aspect of drug abuse and addiction is behavioral sensitization, which is typically seen as a result of repeated exposure to drugs of abuse. The current thesis aimed to further identify the contribution of endogenous opioids to reward and sensitization induced by methamphetamine (METH). It was hypothesized that the opioid antagonist naloxone (NAL) would reduce reward and sensitization induced by METH in rats. Animals were treated for six days to evaluate reward and behavioral sensitization to METH across USVs and locomotor behavior. It was found that initial exposure to METH increased both 50-kHz USVs and locomotor behavior whereas NAL prior to METH dose-dependently attenuated the USV response but had no effect on locomotor behavior. Repeat exposure led to escalations in both USVs and locomotor behavior across treatment days in METH-treated animals, but animals that received NAL prior to METH only displayed increases in locomotor behavior. The administration of a challenge dose of METH revealed no differences in the locomotor or USV response between animals receiving METH for the first time and those that had METH repeatedly; thus METH sensitization did not occur in this study. Similarly METH-induced anticipatory 50-kHz USVs were not observed. Finally, the current studies found that there were no correlations between total 50-kHz USVs and any locomotor behavior suggesting that the two measures may be assessing different aspects of drug reward. The most important finding from this work is that NAL dose-dependently reduced METH-induced reward, suggesting that endogenous opioids are involved in this response. NAL and related compounds may be useful in treatment of METH abuse and addiction.