The effects of ketamine and methamphetamine on neurotransmitters, glutamate receptors, and conditioned place preference in rat

Combined methamphetamine (MA) and ketamine (KET) abuse is a serious issue. At present, however, few studies have explored the mechanism underlying their combined addiction. We established a rat conditioned place preference (CPP) model. We investigated the role of dopamine (DA), 5-hydroxytryptamine (5-HT), monoamine oxidase (MAO), glutamate receptor 1 (GluR1), and glutamate receptor 2 (GluR2) in combined MA and KET addiction. The expression levels of DA, 5-HT, and MAO were detected by enzyme-linked immunosorbent assay (ELISA), and the expressions levels of GluR1 and GluR2 were detected by western blotting. Our results showed that MA and KET successfully induced CPP in rats respectively, and KET enhanced MA-induced CPP effects, although not significantly, and KET can reduce the MA-induced increase in DA, 5-HT, MAO and promoted the MA-induced increase in GluR1 and GluR2. Therefore, it suggested that DA, 5-HT, MAO, GluR1, and GluR2 expression may be involved in the mechanism underlying MA and KET-induced drug addiction in rats. Moreover, When MA and KET are used in combination, KET appears to play a dual addictive and anti-addictive role in the regulation of MA addiction.