Background and Purpose
Monoamine releasers constitute a class of drugs that promote the release of dopamine (DA), serotonin (5-HT) and/or norepinephrine. Although some drugs in this class are well-known drugs of abuse (amphetamine, methamphetamine), others are thought to have reduced (3,4-methylenedioxy-N-methylamphetamine [MDMA]) or no (fenfluramine) abuse potential. The purpose of this study was to further elucidate the role of dopamine versus serotonin selectivity on expression of abuse-related effects produced by monoamine releasers in an assay of intracranial self-stimulation (ICSS) in rats.
Experimental Approach
This study evaluated effects produced in a frequency–rate ICSS procedure by 11 monoamine releasers that vary in selectivity to release DA versus 5-HT.
Key Results
Efficacy of monoamine releasers to facilitate ICSS correlated with DA-selectivity, such that DA-selective releasers exclusively facilitated ICSS, a 5-HT-selective releaser exclusively depressed ICSS, and mixed-action releasers both facilitated low ICSS rates and depressed high ICSS rates. Fixed-proportion mixtures of a DA-selective releaser and a 5-HT-selective releaser recapitulated effects of mixed-action releasers. Efficacy of monoamine releasers to facilitate ICSS also correlated with previously published data on efficacy to maintain self-administration in rhesus monkeys responding under a progressive-ratio schedule of reinforcement.
Conclusions and Implications
These data support the importance of selectivity for DA versus 5-HT in determining abuse potential of monoamine releasers and demonstrate a novel correlation between rat ICSS and nonhuman primate self-administration measures of abuse-related effects. Taken together, these results support the use of ICSS in rats as an experimental tool to study the expression and pharmacological determinants of abuse-related effects of monoamine releasers.
Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats
Bauer, CT., Banks, ML., Blough, B., & Negus, SS. (2013). Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats. British Journal of Pharmacology, 168(4), 850-862. https://doi.org/10.1111/j.1476-5381.2012.02214.x
Abstract
Publications Info
To contact an RTI author, request a report, or for additional information about publications by our experts, send us your request.
Meet the Experts
View All ExpertsRecent Publications
Article
The daily association between affect and alcohol use: A meta-analysis of individual participant data
Article
Protection of forest ecosystems in the eastern United States from elevated atmospheric deposition of sulfur and nitrogen
Article
The use of patient experience feedback in rehabilitation quality improvement and codesign activities
Article