Neurochemical and behavioral differences between d-methamphetamine and d-amphetamine in rats

Abstract

This study reveals several previously unknown neurochemical and behavioral differences between METH and AMPH. Based on these results, it is suggested that new pharmacotherapeutic agents that produce augmentations of NAC GLU or PFC DA activity, or perhaps inhibition of PFC GLU activity, may someday be useful for the treatment of METH addiction.

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

“…Regardless of rearing condition, the acute effect of amphetamine on extracellular glutamate and aspartate levels in the current study is consistent with results from previous microdialysis studies using rats raised in standard housing conditions (Reid et al, 1997;Shoblock et al, 2003;Wolf and Xue, 1999;Xue et al, 1996). However, the underlying mechanism for the enrichment-induced enhancement in amphetamine-induced glutamate and aspartate levels remains unclear.…”

“…Doses represented the salt weight. The doses of amphetamine and MK-801 used in the present study were similar to doses used in previous studies (Shoblock et al, 2003;Xue et al, 1996).…”

“…Although we did not study locomotor activity or behavioral sensitization in relation to glutamate release in NAcc in this report, it is likely that glutamate release has a modulatory role in locomotion via activation of NMDA receptors (Shoblock et al, 2003), as well as via activation of other glutamate receptor subtypes (Giorgetti et al, 2001;Kim and Vezina, 2002). In the current report, the augmented release of glutamate following acute amphetamine in EC rats, which was blocked completely by MK-801, may explain the exaggerated hyperactivity in response to acute amphetamine noted previously in EC rats (Bowling et al, 1993;Bowling and Bardo 1994).…”

“…Acute psychostimulants, including amphetamine, have been shown to increase drug-induced extracellular brain monoamines and excitatory amino acids in the NAcc and other limbic structures (Giogetti et al, 2001;Reid et al, 1997;Shoblock et al, 2003;Xue et al, 1996). Both DA and glutamate are important neurotransmitter systems which could be modulated by environmental manipulations (Pryce at al., 2002).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…While methamphetamine's effects upon the monoaminergic systems have received considerable experimental attention [for reviews, [264][265][266][267][268][269][270], less is known regarding the regulation of corticoaccumbens glutamate and glutamate receptor expression by amphetamine and methylated analogs. Acute administration of amphetamines is reported to produce either no change or a delayed rise in extracellular glutamate levels within striatal regions [59][60][61][62]271,272], while an acute injection of methamphetamine, but not amphetamine, elevates PFC glutamate levels [271]. Whereas repeated cocaine administration produces robust drug-induced glutamate sensitization within the NAC [e.g., 31,35,47,57], repeated dosing with non-toxic regimens of amphetamine or methamphetamine elicits little effect upon the capacity of these drugs to alter glutamate levels within the corticoaccumbens pathway [61,272].…”