TY - JOUR
T1 - Female rats display higher methamphetamine-primed reinstatement and c-Fos immunoreactivity than male rats
AU - Pittenger, Steven T.
AU - Chou, Shinnyi
AU - Murawski, Nathen J.
AU - Barrett, Scott T.
AU - Loh, Olivia
AU - Duque, Juan F.
AU - Li, Ming
AU - Bevins, Rick A.
N1 - Funding Information:
This research was supported in part by NIH research grant DA034389 . RAB was partially supported by DA046109 and GM130461 while preparing this manuscript for publication.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2
Y1 - 2021/2
N2 - Methamphetamine (meth) dependence is often characterized by persistent and chronic relapse (i.e., return to drug use). Previous work suggests females may be at greater risk to relapse. In this study, we extended this limited evidence and identified sex-dependent neural substrates related to meth-triggered reinstatement. Male and female Sprague-Dawley rats were implanted with indwelling jugular catheters. Half of the rats were then trained to self-administer meth (0.05 mg/kg/inf); the other half self-administered saline during 21 daily sessions (2 h). Rats were then given 12 extinction sessions. Twenty-four hours after the last extinction session, rats received reinstatement testing. Half of the rats received a meth-prime (0.3 mg/kg, IP) injection and the remaining rats received a saline injection. This design resulted in 4 separate groups for each sex, allowing for careful investigation of brain regions related to meth-triggered reinstatement. Brains were harvested following the reinstatement session and c-Fos immunoreactivity was measured in multiple brain regions. Meth triggered reinstatement in both sexes and this effect was more robust in females compared to males. Significant sex differences were detected. Females showed greater c-Fos immunoreactivity in the cingulate cortex area 1, lateral orbitofrontal cortex, prelimbic cortex, caudate-putamen, nucleus accumbens core and shell, and central nucleus of the amygdala following meth-primed reinstatement.
AB - Methamphetamine (meth) dependence is often characterized by persistent and chronic relapse (i.e., return to drug use). Previous work suggests females may be at greater risk to relapse. In this study, we extended this limited evidence and identified sex-dependent neural substrates related to meth-triggered reinstatement. Male and female Sprague-Dawley rats were implanted with indwelling jugular catheters. Half of the rats were then trained to self-administer meth (0.05 mg/kg/inf); the other half self-administered saline during 21 daily sessions (2 h). Rats were then given 12 extinction sessions. Twenty-four hours after the last extinction session, rats received reinstatement testing. Half of the rats received a meth-prime (0.3 mg/kg, IP) injection and the remaining rats received a saline injection. This design resulted in 4 separate groups for each sex, allowing for careful investigation of brain regions related to meth-triggered reinstatement. Brains were harvested following the reinstatement session and c-Fos immunoreactivity was measured in multiple brain regions. Meth triggered reinstatement in both sexes and this effect was more robust in females compared to males. Significant sex differences were detected. Females showed greater c-Fos immunoreactivity in the cingulate cortex area 1, lateral orbitofrontal cortex, prelimbic cortex, caudate-putamen, nucleus accumbens core and shell, and central nucleus of the amygdala following meth-primed reinstatement.
KW - Amphetamine
KW - Drug self-administration
KW - Immunohistochemistry
KW - Relapse
KW - c-Fos
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U2 - 10.1016/j.pbb.2020.173089
DO - 10.1016/j.pbb.2020.173089
M3 - Article
C2 - 33422599
AN - SCOPUS:85100222127
SN - 0091-3057
VL - 201
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
M1 - 173089
ER -