| Literature DB >> 32303052 |
Elizabeth M Doncheck1,2, Gage T Liddiard1, Chaz D Konrath1, Xiaojie Liu3, Laikang Yu3, Luke A Urbanik1, Matthew R Herbst1, Margot C DeBaker1, Nicholas Raddatz1, Erik C Van Newenhizen1, Jacob Mathy1, Marieke R Gilmartin1, Qing-Song Liu3, Cecilia J Hillard3, John R Mantsch4.
Abstract
Clinical reports suggest that females diagnosed with substance use disorder experience enhanced relapse vulnerability compared with males, particularly during stress. We previously demonstrated that a stressor (footshock) can potentiate cocaine seeking in male rats via glucocorticoid-dependent cannabinoid type-1 receptor (CB1R)-mediated actions in the prelimbic prefrontal cortex (PrL-PFC). Here, we investigated the influence of biological sex on stress-potentiated cocaine seeking. Despite comparable self-administration and extinction, females displayed a lower threshold for cocaine-primed reinstatement than males. Unlike males, footshock, tested across a range of intensities, failed to potentiate cocaine-primed reinstatement in females. However, restraint potentiated reinstatement in both sexes. While sex differences in stressor-induced plasma corticosterone (CORT) elevations and defensive behaviors were not observed, differences were evident in footshock-elicited ultrasonic vocalizations. CORT administration, at a dose which recapitulates stressor-induced plasma levels, reproduced stress-potentiated cocaine-primed reinstatement in both sexes. In females, CORT effects varied across the estrous cycle; CORT-potentiated reinstatement was only observed during diestrus and proestrus. As in males, CORT-potentiated cocaine seeking in females was localized to the PrL-PFC and both CORT- and restraint-potentiated cocaine seeking required PrL-PFC CB1R activation. In addition, ex vivo whole-cell electrophysiological recordings from female layer V PrL-PFC pyramidal neurons revealed CB1R-dependent CORT-induced suppression of inhibitory synaptic activity, as previously observed in males. These findings demonstrate that, while stress potentiates cocaine seeking via PrL-PFC CB1R in both sexes, sensitivity to cocaine priming injections is greater in females, CORT-potentiating effects vary with the estrous cycle, and whether reactivity to specific stressors may manifest as drug seeking depends on biological sex.Entities:
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Year: 2020 PMID： 32303052 PMCID： PMC7547655 DOI： 10.1038/s41386-020-0674-3
Source DB: PubMed Journal: Neuropsychopharmacology ISSN： 0893-133X Impact factor: 7.853