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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA026258-03
Application #
8008822
Study Section
Special Emphasis Panel (ZRG1-F02A-X (20))
Program Officer
Avila, Albert
Project Start
2008-12-05
Project End
2013-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
3
Fiscal Year
2011
Total Cost
$31,337
Indirect Cost
Name
Albany Medical College
Department
Pharmacology
Type
Schools of Medicine
DUNS #
190592162
City
Albany
State
NY
Country
United States
Zip Code
12208