Activation of metabotropic glutamate receptor 5 is associated with effect of amphetamine on brain neurons

Abstract

The role of metabotropic glutamate receptor 5 (mGluR5) was explored in mechanisms underlying the action of amphetamine (AMPH). The activity of mGluR5 was monitored by measuring the level of [3H]inositol monophosphates in brain neurons, in response to stimulation of 2-choloro-5-hydroxyphenylglycine (CHPG), a selective agonist of mGluR5. Treatment with 1 microM of AMPH for 1 h or 7 days increased the CHPG (1 mM, 30 min)-evoked phosphoinositide turnover by 46% or 92% and 26% or 84% in cultured cortical and hippocampal neurons, respectively, from that of CHPG-only treated cells. When AMPH was present during CHPG application post-1 h or 7 day AMPH incubation, the rate of phosphoinositide hydrolysis in cortical neurons became 121% or 142% higher than that treated with CHPG only. The postnatal day (P) 21 (juvenile) and P60 (adult) rats received three intraperitoneal injections of 5 mg/kg of AMPH or saline daily for 6 days. They were challenged on the eighth day with one dosage and sacrificed 3 h later. Reversible 3H-glutamate binding detected increases of 22-89% in the binding levels of cortex and hippocampus of both ages following the AMPH injections. Increases of 13-18% in the levels of mGluR5 mRNA were seen in the juvenile pyramidal neurons of hippocampal CA1-4, granular cells of dentate gyrus, and ventral thalamic nuclei, as shown by in situ hybridization. The AMPH-induced altered activity of mGluR5 is probably associated with changes in the expression of the glutamate receptors, including mGluR5. AMPH may modify the sensitivity of mGluR5 or interact with the receptor itself.

Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats

“…More generally, group I mGluRs seem to be involved in the mediation of long-term neuroadaptations that occur after repeated cocaine (Ghasemzadeh et al 1999;Swanson et al 2001) and amphetamine administration Yu et al 2003).…”

Bipolar disorder and myo‐inositol: a review of the magnetic resonance spectroscopy findings

“…However, an increase in PME concentrations was seen following d ‐amphetamine administration (58). This is interesting as both human and animal studies have suggested that d ‐amphetamine administration can increase PI‐cycle activity (63–65).…”

Lithium and valproate attenuate dextroamphetamine-induced changes in brain activation

“…Previous studies have confirmed that dextroamphetamine administration acts indirectly to stimulate the PI-cycle (Yu et al, 2003, Silverstone et al, 2002Barkai, 1981). Thus, some of the decrease in brain activation following dextroamphetamine may be mediated via the PI-cycle.…”

“…There is also evidence that dextroamphetamine stimulates the PIcycle (Yu et al, 2003;Silverstone et al, 2002;Barkai, 1981) and this may conceivably be the mechanism responsible for its effects on brain activation. There is also good evidence that both lithium and valproate can attenuate the PI-cycle, probably acting via different mechanisms (Gurvich and Klein, 2002).…”