The effects of lobeline and naltrexone on methamphetamine-induced place preference and striatal dopamine and serotonin levels in adolescent rats with a history of maternal separation.

Abstract	Exposure to early life stress has been suggested to increase an individual's vulnerability to methamphetamine (MA) dependence. Although there is no cure for drug dependence, the opioid and vesicular monoamine transporter 2 (VMAT2) systems may be useful targets for treatment insofar as they play pivotal roles in the neurochemistry of addiction. Here we investigated the effects of naltrexone (opioid antagonist) and lobeline (VMAT2 inhibitor) on MA-induced place preference in adolescent rodents subjected to early life trauma (maternal separation, MS) and controls, as well as the effects on dopamine and serotonin levels in the striatum. We found: (1) maternal separation attenuated methamphetamine-induced place preference; (2) lobeline and naltrexone treatment had differential effects on serotonin and dopamine concentrations in the striatum, naltrexone increased serotonin levels in the maternally separated animals. The hypothesized effect of early adversity increasing MA-induced place preference may not be apparent in adolescence. However the data are consistent with the hypothesis that early life stress influences neurochemical pathways that predispose an individual to drug dependence.
Authors	J J Dimatelis, V A Russell, D J Stein, W M Daniels
Journal	Metabolic brain disease (Metab Brain Dis) Vol. 27 Issue 3 Pg. 351-61 (Sep 2012) ISSN: 1573-7365 [Electronic] United States
PMID	22392627 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Narcotic Antagonists Nicotinic Agonists Slc18a2 protein, rat Vesicular Monoamine Transport Proteins Naltrexone Lobeline
Topics	Age Factors Amphetamine-Related Disorders (drug therapy, metabolism, physiopathology) Animals Animals, Newborn Corpus Striatum (drug effects, growth & development, metabolism) Female Lobeline (pharmacology) Male Maternal Deprivation Naltrexone (pharmacology) Narcotic Antagonists (pharmacology) Nicotinic Agonists (pharmacology) Rats Rats, Sprague-Dawley Stress, Psychological (complications, metabolism, physiopathology) Vesicular Monoamine Transport Proteins (antagonists & inhibitors, metabolism)

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