title: Impaired memory and reduced sensitivity to the circadian period lengthening effects of methamphetamine in mice selected for high methamphetamine consumption.
abstract: Drug abuse runs in families suggesting the involvement of genetic risk factors. Differences in addiction-related neurobiological systems, including learning and memory and circadian rhythms, may exist prior to developing addiction. We characterized the cognitive phenotypes and the free-running circadian period of mouse lines selectively bred for high methamphetamine (MA) drinking (MA high drinking or MAHDR) and low MA drinking (MA low drinking or MALDR). MA-naïve MALDR mice showed spatial memory retention while MAHDR mice did not. MA-naïve MAHDR mice had elevated hippocampal levels of the AMPA receptor subunits GluA2 (old terminology: GluR2), but not GluA1 (old terminology: GluR1). There were no line differences in the free running period (τ) when only water was available. During a 25 mg/L MA solution access period (vs water), there was an increase in τ in MALDR but not MAHDR mice, although MAHDR mice consumed significantly more MA. During a 50 mg/L MA solution access period (vs water), both lines showed an increased τ. There was a positive correlation between MA consumption and τ from baseline in MALDR, but not MAHDR, mice. Thus, a heritable proclivity for elevated MA self-administration may be associated with impairments in hippocampus-dependent memory and reduced sensitivity to effects of MA on lengthening of the circadian period.
authors: Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors: Reid H J
authors: RH
authors: Olsen
authors: Charles N
authors: CN
authors: Allen
authors: Victor A
authors: VA
authors: Derkach
authors: Tamara J
authors: TJ
authors: Phillips
authors: John K
authors: JK
authors: Belknap
authors: Jacob
authors: J
authors: Raber
mesh_terms: D019969:Amphetamine-Related Disorders / Q000503:physiopathology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002940:Circadian Rhythm; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009043:Motor Activity; D018091:Receptors, AMPA / Q000378:metabolism*; D012646:Self Administration; D013045:Species Specificity
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Circadian; GluA1/2; Glutamate receptors; Methamphetamine; Spatial memory; Water maze
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