title: Repeated administration of the 5-HT₁B/₁A agonist, RU 24969, facilitates the acquisition of MDMA self-administration: role of 5-HT₁A and 5-HT₁B receptor mechanisms.
abstract: BACKGROUND
  3,4 Methylenedioxymethamphetamine (MDMA) preferentially stimulates the release of serotonin (5-HT) that subsequently produces behavioral responses by activation of post-synaptic receptor mechanisms. The 5-HT1A and 5-HT1B receptors are both well localized to regulate dopamine (DA) release, and have been implicated in modulating the reinforcing effects of many drugs of abuse, but a role in acquisition of self-administration has not been determined.
  
  
  OBJECTIVE
  This study was designed to determine the effect of pharmacological manipulation of 5-HT1A and 5-HT1B receptor mechanisms on the acquisition of MDMA self-administration.
  
  
  METHODS
  The 5-HT1B/1A receptor agonist, RU 24969 (0.0 or 3.0 mg/kg, bid), was administered for 3 days in order to down-regulate both 5-HT1A and 5-HT1B receptors. Following the pretreatment phase, latency to acquisition of MDMA self-administration was measured.
  
  
  RESULTS
  Repeated administration of RU 24969 significantly decreased the latency to acquisition and increased the proportion of animals that acquired MDMA self-administration. Dose-effect curves for the 5-HT1A-mediated hyperactivity produced by the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT1B-mediated adipsic response produced by RU 24969 were shifted rightward, suggesting a desensitization of 5-HT1A and 5-HT1B receptor mechanisms.
  
  
  CONCLUSIONS
  These data suggest that the initial reinforcing effects of MDMA are modulated by 5-HT1A and/or 5-HT1B receptor mechanisms. The potential impact of these changes on the DAergic response relevant to self-administration and a possible role in conditioned reinforcement pertaining to acquisition of self-administration are discussed.
authors: School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.
authors: Dane
authors: D
authors: Aronsen
authors: School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.
authors: Natasha
authors: N
authors: Bukholt
authors: School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand. Susan.schenk@vuw.ac.nz.
authors: Susan
authors: S
authors: Schenk
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012646:Self Administration; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D007211:Indoles; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: 5-HT1A; 5-HT1B; Acquisition; Dopamine; MDMA; RU 24969; Self-administration; Serotonin