title: 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.affiliation: Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa. jacqueline.dimatelis@gmail.com
authors.forename: J J
authors.initials: JJ
authors.lastname: Dimatelis
authors.forename: V A
authors.initials: VA
authors.lastname: Russell
authors.forename: D J
authors.initials: DJ
authors.lastname: Stein
authors.forename: W M
authors.initials: WM
authors.lastname: Daniels
mesh_terms: D000367:Age Factors; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D008120:Lobeline / Q000494:pharmacology*; D008297:Male; D008426:Maternal Deprivation; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D009271:Naltrexone; D008120:Lobeline