Individual and Combined Effects of Methamphetamine and Ketamine on Conditioned Place Preference and NR1 Receptor Phosphorylation in Rats

Abstract

Methamphetamine (MA), a commonly abused psychostimulant, induces the drug dependence by enhancing the dopamine-mediated neurotransmission. Ketamine (KET) is a non-competitive N-methyl-D-aspartate receptor antagonist, which can be actually mixed with MA for polydrug abuse. In the present study, the individual and combined effects of KET (10 mg/kg, i.p.) and MA (1 mg/kg, i.p.) on conditioned place preference in rats were investigated. The alterations of serine 897 phosphorylations of NR1 receptors in the striatum and ventral tegmental area of after-conditioning rats were measured immunochemically. The results showed repeated administrations of MA, KET and their combination, at the doses studied, all could induce psychological dependences evaluated by conditioned place preference. KET was not able to suppress the MA-induced place preference. The modulations of NR1 phosphorylations in basal ganglia were partly responsible to place preference. Although the alterations induced by KET were not significant in most areas we studied, MA showed a significant increase in the ventral tegmental area but a marked decrease in caudate putamen and nucleus accumbens. Such alterations were much more significant when KET and MA were combined. These results have important implications for public awareness of harm with combined drug abuse. Further investigations toward the specific interaction of the two drugs are necessary.

Levo-tetrahydropalmatine inhibits the acquisition of ketamine-induced conditioned place preference by regulating the expression of ERK and CREB phosphorylation in rats

“…In the present study, ketamine (5, 10 and 15 mg/kg, i. p.) induced CPP in the rats. This conclusion is consistent with that described in previous studies [35][36][37]. Besides, we found that l-THP (1.25, 2.5, 5.0, 10.0, 20.0 mg/kg, i.p.)…”

Combining Ketamine with Astrocytic Inhibitor as a Potential Analgesic Strategy for Neuropathic Pain. Ketamine, Astrocytic Inhibitor and Pain

“…As a functional subunit of NMDAR, NR1 phosphorylation is significantly increased in the ipsilateral spinal cord after nerve injury and coincides with mechanical allodynia [28]. Previous study suggests that ketamine combined with methamphetamine could down-regulate NR1 receptor phosphorylation in rats (phosphorylation site: serine 897) [29]. Moreover, it is reported that NR1 subunit knockout mice are more resistant to ketamine than control wide type mice, indicating that NMDAR NR1 subunit contributes to mediation of ketamine anesthesia or analgesia [30].…”

Lobelane Inhibits Methamphetamine-Evoked Dopamine Release via Inhibition of the Vesicular Monoamine Transporter-2

“…There are currently no approved medications to treat methamphetamine abuse. Methamphetamine abuse liability stems from its reinforcing and rewarding effects demonstrated by use of animal models of intravenous methamphetamine self-administration and conditioned place preference, respectively (Yokel and Pickens, 1973;Hart et al, 2001, Xu et al, 2008. Brain dopaminergic pathways are activated by methamphetamine (Di Chiara and Imperato, 1988;Gold et al, 1989;Wise, 2002).…”