TY - JOUR
T1 - Effects of neonatal methamphetamine and thioperamide exposure on spatial memory retention and circadian activity later in life
AU - Eastwood, Emily
AU - Allen, Charles N.
AU - Raber, Jacob
N1 - Funding Information:
This work was supported by National Institute of Drug Abuse T32DA07262 (KN), NS036607 (CNA), Methamphetamine Abuse Research Center Grant 1P50DA018165 (AJ), and the development account of Dr. Raber.
PY - 2012/4/21
Y1 - 2012/4/21
N2 - 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.
AB - 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.
KW - Adolescence
KW - Circadian
KW - Cognition
KW - Hippocampus
KW - Methamphetamine
KW - Postnatal
KW - Thioperamide
UR - http://www.scopus.com/inward/record.url?scp=84857683080&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857683080&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2012.02.003
DO - 10.1016/j.bbr.2012.02.003
M3 - Article
C2 - 22330947
AN - SCOPUS:84857683080
SN - 0166-4328
VL - 230
SP - 229
EP - 236
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -