In 2004 approximately 74,000 emergency room visits and over 150,000 hospital admissions were attributed to methamphetamine (METH) abuse. Accordingly, the need for effective METH abuse therapies is paramount. Cannabinoid receptor (CB1) antagonists attenuate both METH self-administration and METH- induced behavioral sensitization in rodents. Thus, endogenous cannabinoid transmission is a potential therapeutic target for METH abuse. Despite robust behavioral evidence, little neurophysiological data exist substantiating CB1 modulation of METH abuse. To address this, 3 experimental aims are proposed:
Aim 1 : To determine neurochemical and electrophysiological correlates of METH psychomotor activation. We hypothesize that METH activation is temporally coincident with both augmented, sub-second dopaminergic transmission and altered electrophysiological profiles in the NAc. Spontaneous, sub-second dopamine release, multiple single-unit activity and local field potentials will be recorded in the nucleus accumbens (NAc) of freely-moving rats during intravenous METH administration to validate this hypothesis.
Aim 2 : To determine the effect of rimonabant on METH psychomotor activation and its correlates in the NAc. We hypothesize that the CB1 antagonist/ inverse agonist rimonabant attenuates METH psychomotor activation and its neurophysiological correlates in the NAc. Subjects pretreated with either rimonabant or vehicle will be subjected to a similar experimental design as described in Aim 1 to support this hypothesis.
Aim 3 : To determine the effect of rimonabant on METH psychomotor sensitization expression and its correlates in the NAc. We hypothesize that the neurophysiological correlates of METH activation are enhanced in sensitized animals. We further hypothesize that rimonabant attenuates expression of this enhancement. Animals sensitized to METH will be subjected to similar experimental protocols as described in Aims 1 and 2 to validate this hypothesis.
|Morra, Joshua T; Glick, Stanley D; Cheer, Joseph F (2012) Cannabinoid receptors mediate methamphetamine induction of high frequency gamma oscillations in the nucleus accumbens. Neuropharmacology 63:565-74|
|Morra, Joshua T; Glick, Stanley D; Cheer, Joseph F (2010) Neural encoding of psychomotor activation in the nucleus accumbens core, but not the shell, requires cannabinoid receptor signaling. J Neurosci 30:5102-7|