title: Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Bauer
authors.forename: M L
authors.initials: ML
authors.lastname: Banks
authors.forename: B E
authors.initials: BE
authors.lastname: Blough
authors.forename: S S
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism*; D046690:Deep Brain Stimulation; D004305:Dose-Response Relationship, Drug; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012653:Self Stimulation; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000523:psychology
chemical_list: D015306:Biogenic Monoamines; D013287:Illicit Drugs