Sex differences exist in drug abusing populations. In addition, it has been shown that the female gonadal hormones, estrogen and progesterone, modulate behavior elicited by cocaine in different and sometimes opposite ways. The primary aim of the proposed research is to examine the effects of progesterone on the inhibition of cocaine-seeking behavior in rats. In the proposed research, the effectiveness of progesterone as a treatment will be examined in the escalation and maintenance phases of the addiction process. The self-administration paradigm will be used to asses these effects. The following are specific aims that correspond to the 3 proposed self-administration experiments:
Aim 1 - to examine the influence of progesterone treatment in male and female rats on responding under a progressive ratio schedule and during escalation of drug intake due to extended access. The effects of progesterone treatment on nondrug reinforcers will also be examined to assess progesterone's therapeutic specificity.
Aim 2 - to assess the therapeutic effectiveness of progesterone as a treatment in populations that differ in the vulnerability to cocaine-seeking behavior. These populations include: male vs. female, high vs. low impulsive, and high vs. low saccharin preferring rats.
Aim 3 - to examine the effects of one of progesterone's behaviorally active, metabolites, allopregnanolone, during the escalation of cocaine intake. The proposed research will also assess the effectiveness of progesterone and allopregnanolone as potential treatments for cocaine abuse in more and less vulnerable phenotypes. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA023301-02
Application #
7503357
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Avila, Albert
Project Start
2007-09-28
Project End
2010-09-27
Budget Start
2008-09-28
Budget End
2009-09-27
Support Year
2
Fiscal Year
2008
Total Cost
$35,363
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Psychiatry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Anker, Justin J; Holtz, Nathan A; Carroll, Marilyn E (2012) Effects of progesterone on escalation of intravenous cocaine self-administration in rats selectively bred for high or low saccharin intake. Behav Pharmacol 23:205-10
Anker, Justin J; Baron, Thomas R; Zlebnik, Natalie E et al. (2012) Escalation of methamphetamine self-administration in adolescent and adult rats. Drug Alcohol Depend 124:149-53
Anker, Justin J; Zlebnik, Natalie E; Navin, Sean F et al. (2011) Responding during signaled availability and nonavailability of iv cocaine and food in rats: age and sex differences. Psychopharmacology (Berl) 215:785-99
Anker, Justin J; Carroll, Marilyn E (2011) Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake. Drug Alcohol Depend 118:68-72
Gosnell, Blake A; Mitra, Anaya; Avant, Ross A et al. (2010) Operant responding for sucrose by rats bred for high or low saccharin consumption. Physiol Behav 99:529-33
Anker, Justin J; Carroll, Marilyn E (2010) Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats. Psychopharmacology (Berl) 208:211-22
Zlebnik, Natalie E; Anker, Justin J; Gliddon, Luke A et al. (2010) Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats. Psychopharmacology (Berl) 209:113-25
Anker, Justin J; Zlebnik, Natalie E; Carroll, Marilyn E (2010) Differential effects of allopregnanolone on the escalation of cocaine self-administration and sucrose intake in female rats. Psychopharmacology (Berl) 212:419-29
Anker, Justin J; Carroll, Marilyn E (2010) The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research. Neurosci Biobehav Rev 35:315-33
Anker, Justin J; Carroll, Marilyn E (2010) Sex differences in the effects of allopregnanolone on yohimbine-induced reinstatement of cocaine seeking in rats. Drug Alcohol Depend 107:264-7

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