title: Effects of chronic methamphetamine on psychomotor and cognitive functions and dopamine signaling in the brain.
abstract: Methamphetamine (MA) studies in animals usually involve acute, binge, or short-term exposure to the drug. However, addicts take substantial amounts of MA for extended periods of time. Here we wished to study the effects of MA exposure on brain and behavior, using an animal model analogous to this pattern of MA intake. MA doses, 4 and 8mg/kg/day, were based on previously reported average daily freely available MA self-administration levels. We examined the effects of 16 week MA treatment on psychomotor and cognitive function in the rat using open field and novel object recognition tests and we studied the adaptations of the dopaminergic system, using in vitro and in vivo receptor imaging. We show that chronic MA treatment, at doses that correspond to the average daily freely available self-administration levels in the rat, disorganizes open field activity, impairs alert exploratory behavior and anxiety-like state, and downregulates dopamine transporter in the striatum. Under these treatment conditions, dopamine terminal functional integrity in the nucleus accumbens is also affected. In addition, lower dopamine D1 receptor binding density, and, to a smaller degree, lower dopamine D2 receptor binding density were observed. Potential mechanisms related to these alterations are discussed.
authors.affiliation: Behavioral Neuropharmacology & Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA. Electronic address: pthanos@ria.buffalo.edu.
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.affiliation: Behavioral Neuropharmacology & Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, 45100, Greece.
authors.forename: Foteini
authors.initials: F
authors.lastname: Delis
authors.affiliation: Behavioral Neuropharmacology & Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rocco
authors.affiliation: Behavioral Neuropharmacology & Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, 45100, Greece; Laboratory of Neuroimaging, Intramural Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001552:Benzazepines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D020891:Raclopride / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D002247:Carbon Isotopes; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; C534628:SCH 23390; D020891:Raclopride; D008694:Methamphetamine; D013134:Spiperone; D004298:Dopamine
keywords: Behavior; Brain; Chronic; Dopamine; Methamphetamine; Positron emission tomography; Reward deficiency syndrome