Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone.
Impulsive choice, or an inability to delay immediate gratification, has been strongly linked to the development and persistence of drug abuse. Indeed, delaying drug use itself may underlie drug addiction and relapse. Thus, employing treatments that are efficacious in reducing impulsive choice (atomoxetine; ATO) or drug-seeking behavior (progesterone; PRO) may be an effective means of treating drug addiction.



The current study assessed sex differences in the effects of PRO, ATO, and their combination in a delay discounting paradigm for cocaine and for sucrose pellets.



Male and female rats chose between a small-immediate or a large-delayed (0, 7.5, 15, 30, 60 s) outcome in an impulsive choice procedure for sucrose pellets (1 vs. 3 pellets) or for iv cocaine infusions (0.3 vs. 0.9 mg/kg). Following baseline assessment of impulsive choice, rats received daily treatment of vehicle (VEH), PRO (0.5 mg/kg), ATO (1.5 mg/kg), or a combination (PRO + ATO) until a second assessment of impulsive choice was determined.



Compared to the VEH group, females were less impulsive for cocaine following PRO or the PRO + ATO combined treatment, whereas males were less impulsive for cocaine following ATO. No treatment effects were observed on impulsive choice for sucrose pellets.



The present results indicate that impulsive choice for cocaine is reduced by PRO in females and by ATO in males. These findings suggest both treatments may be an effective intervention in treating cocaine abuse, but that their effectiveness differs by sex.
Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA. jsmethells@gmail.com.
John R
JR
Smethells
Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA.
Natashia L
NL
Swalve
Division of Biostatistics, University of Minnesota, Minneapolis, MN, 55455, USA.
Lynn E
LE
Eberly
Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA.
Marilyn E
ME
Carroll
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D065786:Delay Discounting / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005260:Female; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D012737:Sex Factors; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage
D018759:Adrenergic Uptake Inhibitors; D018765:Dopamine Uptake Inhibitors; D011372:Progestins; D013549:Sweetening Agents; D011374:Progesterone; D013395:Sucrose; D000069445:Atomoxetine Hydrochloride; D003042:Cocaine
Cocaine; Delay discounting; Female; Impulsive choice; Rats; Recreational drug use