TY - JOUR
T1 - N-acetylcysteine yields sex-specific efficacy for cue-induced reinstatement of nicotine seeking
AU - Goenaga, Julianna
AU - Powell, Gregory L.
AU - Leyrer-Jackson, Jonna M.
AU - Piña, Jose
AU - Phan, Sandy
AU - Prakapenka, Alesia V.
AU - Koebele, Stephanie V.
AU - Namba, Mark D.
AU - McClure, Erin A.
AU - Bimonte-Nelson, Heather A.
AU - Gipson, Cassandra D.
N1 - Publisher Copyright:
© 2019 Society for the Study of Addiction
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Women report greater craving during certain phases of the menstrual cycle. As well, research indicates that pharmacotherapies for smoking may be less efficacious in women compared with men, which may be due to interactions with natural fluctuations in ovarian hormone levels. N-Acetylcysteine (NAC) is a glutamatergic compound that has shown some efficacy in treating substance use disorders and aids in the prevention of relapse. However, it is unclear whether NAC has sex-specific effectiveness for nicotine relapse treatment. Given that NAC has shown promise to reduce nicotine reinstatement in preclinical models using male rats, the exploration of potential sex differences in the efficacy of NAC is warranted. Using a rat model, we first investigated the ability of NAC treatment (100 mg/kg, ip) during nicotine withdrawal with extinction training to reduce cue-induced nicotine seeking in male and female rats. Next, we assessed whether NAC's effects were estrous cycle–dependent for female rats. Results show that following NAC treatment during extinction, reinstatement of nicotine seeking was significantly decreased in males but not females, indicating a sex-specific effect of NAC. Furthermore, for females, both vehicle- and NAC-treated groups significantly reinstated nicotine-seeking behavior compared with extinction, regardless of estrous cycle phase. These results suggest that NAC is inefficacious in reducing nicotine relapse in females regardless of estrous cycle phase at the dose evaluated here. These collective findings could have important clinical implications for use and efficacy of NAC as a pharmacotherapy for freely cycling women smokers.
AB - Women report greater craving during certain phases of the menstrual cycle. As well, research indicates that pharmacotherapies for smoking may be less efficacious in women compared with men, which may be due to interactions with natural fluctuations in ovarian hormone levels. N-Acetylcysteine (NAC) is a glutamatergic compound that has shown some efficacy in treating substance use disorders and aids in the prevention of relapse. However, it is unclear whether NAC has sex-specific effectiveness for nicotine relapse treatment. Given that NAC has shown promise to reduce nicotine reinstatement in preclinical models using male rats, the exploration of potential sex differences in the efficacy of NAC is warranted. Using a rat model, we first investigated the ability of NAC treatment (100 mg/kg, ip) during nicotine withdrawal with extinction training to reduce cue-induced nicotine seeking in male and female rats. Next, we assessed whether NAC's effects were estrous cycle–dependent for female rats. Results show that following NAC treatment during extinction, reinstatement of nicotine seeking was significantly decreased in males but not females, indicating a sex-specific effect of NAC. Furthermore, for females, both vehicle- and NAC-treated groups significantly reinstated nicotine-seeking behavior compared with extinction, regardless of estrous cycle phase. These results suggest that NAC is inefficacious in reducing nicotine relapse in females regardless of estrous cycle phase at the dose evaluated here. These collective findings could have important clinical implications for use and efficacy of NAC as a pharmacotherapy for freely cycling women smokers.
KW - N-acetylcysteine
KW - estrous cycle
KW - nicotine
KW - sex differences
KW - smoking
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U2 - 10.1111/adb.12711
DO - 10.1111/adb.12711
M3 - Article
C2 - 30734439
AN - SCOPUS:85061255956
SN - 1355-6215
VL - 25
JO - Addiction Biology
JF - Addiction Biology
IS - 1
M1 - e12711
ER -