Item Details

title

FACTORS THAT AFFECT SOCIAL HIERARCHY AND THE INFLUENCE OF SOCIAL RANK AND MENSTRUAL CYCLE ON COCAINE SELF-ADMINISTRATION IN FEMALE CYNOMOLGUS MONKEYS

author

Riddick, Natallia

abstract

Accumulating evidence from both preclinical and clinical studies suggests that women may have a greater biological vulnerability to cocaine addiction than males. Studying behavioral, neurochemical, neurobiological or physiological trait and state variables may provide some insight into individual difference leading to high risk for drug abuse. The research described in this dissertation was designed to examine a number of trait and state markers associated with social hierarchy in female nonhuman primates. In addition, the effect of menstrual cycle phase and social rank was examined on acquisition and maintenance of cocaine reinforcement. Chapter II was aimed at examining physiological, neurochemical, neuropharmacological and behavioral variables that may be associated with social rank. The two measures that correlated with social rank were cerebrospinal fluid concentrations of the 5-HT metabolite 5-HIAA, which were significantly higher in the animals that eventually became subordinate and latency to touch a novel object, which was significantly lower in eventual subordinate monkeys. Age, body weight, locomotor activity in a novel environment, HPA-axis function and peripheral serotonin (5-HT) activity, as measured in blood and central 5-HT activity, as measured with brain imaging, did not predict social rank and did not change after stable social group formations. These data suggest that levels of central 5-HIAA and measures of novel object reactivity may be trait markers that influence eventual social rank in female macaques. The studies in Chapter III examined the influence of social rank and menstrual cycle phase on acquisition and maintenance of cocaine self-administration in socially housed female monkeys. Dominant monkeys appeared more sensitive to the reinforcing effects of cocaine, with over 60% acquiring self-administration at the lowest dose (0.001 mg/kg) compared to ~ 20% subordinate monkeys. At higher cocaine doses, there were no differences in rates of acquisition. In maintenance, the peak of the cocaine dose-response curve for dominant monkeys was to the left of those for subordinate monkeys. Finally, menstrual cycle phase did not affect cocaine sensitivity in dominant or subordinate monkeys. These studies are at odds with earlier work in male monkeys and suggest that dominant female monkeys are more vulnerable to cocaine reinforcement than subordinate monkeys. These findings highlight the importance of sex differences in animal models of cocaine abuse. In conclusion, the research presented in this dissertation further extends our understanding of the neurobiological and behavioral underpinnings of social rank and cocaine reinforcement and extends the work to female monkeys. The findings suggest a gender-specific “vulnerable” phenotype for cocaine reinforcement. Further studies of social rank-related differences in neurobiology and other individual traits are warranted to better understand vulnerability to drug abuse in females which could lead to identification of potential new targets for pharmacological and behavioral therapies of cocaine abuse.

subject

cocaine self-administration, menstrual cycle, females, imaging, neurobiology, cocaine sensitivity

contributor

Jay R. Kaplan, Ph.D. (committee chair)

Paul W. Czoty, Ph.D. (committee member)

J. Charles Eldridge, Ph.D. (committee member)

Linda J. Porrino, Ph.D. (committee member)

Michael A. Nader, Ph.D. (committee member)

date

2009-03-19T14:20:04Z (accessioned)

2010-06-18T19:00:02Z (accessioned)

2009-03-19T14:20:04Z (available)

2010-06-18T19:00:02Z (available)

2009-03-19T14:20:04Z (issued)

degree

Pharmacology (discipline)

identifier

http://hdl.handle.net/10339/14914 (uri)

language

en_US (iso)

publisher

Wake Forest University

rights

Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)

type

Dissertation