Premium
Sex Differences in Cocaine Self‐Administration Behavior are Driven by Estrous Stage Dependent Changes in Dopamine Transporter Sensitivity to Cocaine
Author(s) -
MAUTERER MADELYN,
Jones Sara R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.681.5
Subject(s) - estrous cycle , psychology , dopamine , self administration , craving , abstinence , physiology , conditioned place preference , estrogen , addiction , developmental psychology , medicine , endocrinology , neuroscience , psychiatry
Traditionally, preclinical cocaine studies have focused primarily on male behavior and neurobiology, but recent work has suggested that there are distinct differences in male versus female cocaine responsivity. In humans, progression to cocaine dependence is faster in women compared to men. Women also exhibit greater craving and relapse following abstinence. Similar to humans, rodent literature suggests males and females have differential behavioral responses to cocaine, which appear to be estrous cycle dependent. For example, females exposed to cocaine during the estrous phase exhibit augmented behavioral responses, such as increased conditioned place preference and greater cocaine seeking. Furthermore, recent literature has uncovered neurobiological differences between the sexes, specifically related to estrogen, which suggest that differences within the dopamine system, specifically, may underlie the observed increase in cocaine abuse vulnerability in females. Here, we used intravenous cocaine self‐administration to assess differences in time to acquire and motivation to seek cocaine between not only sex but also stages of the estrous cycle. We found that female rats are most likely to achieve cocaine self‐administration acquisition parameters when they are in the estrus phase of the cycle; in fact, 90% of females tested were in the estrus phase at time of acquisition. We used the threshold schedule of reinforcement, a paradigm of behavioral economics, to assess motivation to take cocaine. Females in estrus exhibit greater motivation (increased “price” paid to maintain blood cocaine levels; Pmax) which is augmented further if their first exposure to cocaine occurred during estrus as well. Our observed behavioral differences were further shown to be correlated with changes in dopamine terminal sensitivity. Using ex vivo fast scan cyclic voltammetry (FSCV) in the nucleus accumbens (NAc), we found that females in estrus show greater terminal sensitivity to cocaine which may drive the increased cocaine taking behaviors. Support or Funding Information R01 DA014030 T32 AA007565 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .