Full metadata
Title
Serotonin 1B Receptor Modulation of cocaine Abuse-Like Behavior in Female Rats Before and After Abstinence from Self-Administration
Description
Serotonin 1B receptors (5-HT1BRs) are involved in cocaine reward via regulating activity of dopamine neurons. The 5-HT1BR agonist CP-94,253 or 5-HT1BR overexpression in the nucleus accumbens shell (NAcSh) enhances cocaine intake during maintenance of daily self-administration (SA) but inhibits intake after 21 days of abstinence in male rats. My central hypothesis is that CP-94,253 acts at 5-HT1BRs located on the terminals of NAcSh GABA neurons that undergo regulatory changes in response to cocaine SA and subsequent abstinence resulting in an abstinence-induced switch in the functional effects of CP-94,253 in both male and female rats. In the first series of experiments, I compared the functional effects of CP-94,253 in female rats to male rats: 1) during maintenance of daily cocaine SA, 2) after 21-60 days abstinence, and 3) during the resumption of cocaine SA after abstinence (i.e. model of relapse). I found that CP-94,253 enhanced cocaine intake and breakpoints on a high-effort progressive ratio schedule of cocaine reinforcement during maintenance regardless of sex. By contrast, CP-94,253 attenuated cocaine intake after 21 days of abstinence and during the relapse test, regardless of sex. These findings suggest: 1) an abstinence-induced inhibitory effect of the 5-HT1BR agonist occurs in both sexes, 2) these inhibitory effects are long-lasting, and 3) the agonist may provide a novel therapeutic for cocaine use disorders. I next used RNAscope in situ hybridization to measure regulatory changes in 5-HT1BR mRNA expression and its co-expression with GABAergic and glutamatergic cell markers in the lateral and medial NAcSh subregions after abstinence from cocaine. I found no significant changes in these measures in either subregion of NAcSh after prolonged abstinence in either sex; however, I did observe that 95% of 5-HT1BR mRNA is co-localized in GABAergic neurons, whereas <2% is co-localized in glutamatergic cells. Future research investigating abstinence-induced, functional changes in 5-HT1BRs in subregions of the NAcSh is an alternate approach to further test my hypothesis. This research is important for the development of 5-HT1BR agonists as putative treatments of cocaine use disorders.
Date Created
2024
Contributors
- Scott, Samantha N (Author)
- Neisewander, Janet L (Thesis advisor)
- Newbern, Jason (Committee member)
- Olive, Michael F (Committee member)
- Sanabria, Federico (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
191 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.2.N.193683
Level of coding
minimal
Cataloging Standards
Note
Partial requirement for: Ph.D., Arizona State University, 2024
Field of study: Neuroscience
System Created
- 2024-05-02 02:39:33
System Modified
- 2024-05-02 02:39:40
- 6 months 1 week ago
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