Item Details

title

A NONHUMAN PRIMATE MODEL OF COCAINE-ALCOHOL POLYSUBSTANCE ABUSE: EFFECTS ON DOPAMINE RECEPTORS AND PUTATIVE MEDICATIONS

author

Say, Felicity Machaela Camri

abstract

Although most individuals with cocaine use disorder co-abuse alcohol, little is known about the behavioral and pharmacological mechanisms that underlie this co-abuse. Previous studies have documented that chronic use of alcohol or cocaine decreases dopamine D2-like receptor (D2R) availability and increases dopamine D3 receptor (D3R) function. However, the effects of cocaine and alcohol co-abuse have not been studied. As a result, this study examined long-term cocaine self-administration in rhesus monkeys with or without daily ethanol consumption. Twelve adult male monkeys self-administered cocaine (0.1 mg/kg/inj) on an FR30 schedule 5 days/week. Half of these monkeys modeled binge-like drinking while the other half served as controls and received no access to alcohol. D2R availability was examined via PET scans when monkeys were drug-naive and after monkeys had self-administered 400 mg/kg cocaine. To measure the function of D3R, quinpirole-induced yawning was accessed at the same time points. Moreover, acute buspirone treatments were given to both groups (N=4) to examine its effects on cocaine self-administration. Chronic cocaine self-administration decreased D2R availability, particularly in the putamen. However, this effect was not observed in monkeys who consumed ethanol. In contrast, the potency of quinpirole was increased in ethanol-drinking monkeys, whereas no change was observed in the control group, indicating an increased sensitivity of D3R in ethanol drinkers. These results suggest that chronic alcohol use can modulate the effects of cocaine on dopamine receptor function and that its effects on D3R are likely involved in promoting co-abuse. The results also suggest that buspirone does not decrease cocaine self-administration in the presence or absence of alcohol. Further research should be conducted using other putative D3R selective medications that have a history of decreasing cocaine SA.

subject

drug self-administration

ethanol

Non-human primates

polysubstance abuse

contributor

Czoty, Paul (committee chair)

Holleran, Katherine (committee member)

date

2022-05-24T08:36:15Z (accessioned)

2023-05-23T08:30:14Z (available)

2022 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2023-05-23 (terms)

identifier

http://hdl.handle.net/10339/100775 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis