Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 320, Issue -, Pages 282-290Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2016.12.010
Keywords
Chronic; Methamphetamine; Dopamine; Behavior; Brain; Reward deficiency syndrome; Positron emission tomography
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Funding
- Research Foundation of New York
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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 8 mg/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. (C) 2016 Published by Elsevier B.V.
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