title: Effects of neonatal methamphetamine and thioperamide exposure on spatial memory retention and circadian activity later in life.
abstract: Methamphetamine (MA) use increases the likelihood of engaging in risky sexual behavior and most MA-using women are of child-bearing age. Therefore, cognitive effects following MA exposure to the developing brain are concerning. Exposure of mice to MA during hippocampal development causes cognitive impairments in adulthood. These effects are more severe in female than male mice and mimicked by the H(3) receptor antagonist thioperamide (THIO). In this study, we assessed whether neonatal exposure to MA or THIO also affects cognition in adolescence. As these effects might be associated with alterations in circadian activity, we also assessed circadian activity in a subgroup of neonatally exposed mice. Sex-dependent treatment effects were seen in the water maze. While THIO-, but not MA-treated female mice showed hippocampus-dependent spatial memory retention in the first probe trial, MA-, but not THIO-treated female mice showed spatial memory retention in the probe trial following reversal training. In contrast, MA- and THIO-treated male mice showed spatial memory retention in both probe trials. When sensorimotor gating was assessed, MA-treated male mice showed greater pre-pulse inhibition than MA-treated female mice. Regardless of sex, THIO-treated mice gained on average more weight each day and showed an enhanced startle response. In addition, MA increased the length of the circadian period, with an intermediate effect following THIO treatment were observed. No treatment effects in exploratory behavior, measures of anxiety, or contextual or cued fear conditioning. Thus, the water maze is particularly sensitive to detect sex-dependent effects of neonatal MA and THIO exposure on spatial memory retention in adolescence.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, 8131 SW Sam Jackson Park Road, Portland, OR 97239, USA. eastwooe@ohsu.edu
authors.forename: Emily
authors.initials: E
authors.lastname: Eastwood
authors.forename: Charles N
authors.initials: CN
authors.lastname: Allen
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D003463:Cues; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology*; D012153:Retention, Psychology / Q000187:drug effects*; D055139:Sensory Gating / Q000187:drug effects; D012737:Sex Factors; D013037:Spatial Behavior / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D054828:Histamine H3 Antagonists; D010880:Piperidines; D008694:Methamphetamine; C052075:thioperamide