title: Dopaminergic mechanisms of reinstatement of MDMA-seeking behaviour in rats.
abstract: OBJECTIVE
  Animal models of drug-seeking suggest that exposure to cues associated with self-administered drugs and drug primes might precipitate relapse via activation of central dopaminergic substrates.
  
  
  METHODS
  The effects of priming injections of dopamine and 5-HT agonists on drug-seeking and effects of dopamine antagonists on methylenedioxymethamphetamine (MDMA)-produced potentiation of drug-seeking following extinguished MDMA self-administration were examined.
  
  
  RESULTS
  Drug-seeking was produced by exposure to a light stimulus that had been paired with self-administered MDMA infusions and this effect was potentiated by experimenter-administered injections of the dopamine D(2) -like receptor agonist, quinpirole, the indirect agonist, amphetamine and the uptake inhibitor, GBR 12909. Drug-seeking was not elicited by the dopamine D(1) -like receptor agonist, SKF 81297 or the non-selective agonist, apomorphine. The 5-HT receptor agonists DOI or mCPP also failed to elicit drug-seeking. The 5-HT uptake inhibitor, clomipramine, attenuated drug-seeking produced by the MDMA-associated stimulus but failed to alter the potentiated response produced by GBR 12909. The D(1) receptor antagonist, SCH 23390 or the D(2) receptor antagonist, eticlopride attenuated the potentiation of drug-seeking produced by MDMA.
  
  
  CONCLUSIONS
  These data provide evidence of dopaminergic mechanisms in drug-seeking following extinction of MDMA self-administration. Because tissue levels of 5-HT were significantly decreased following MDMA self-administration, we suggest that MDMA begins to preferentially activate dopaminergic substrates to potentiate the drug-seeking response.
authors.affiliation: Victoria University of Wellington, School of Psychology, Wellington, New Zealand. susan.schenk@vuw.ac.nz
authors.forename: S
authors.initials: S
authors.lastname: Schenk
authors.forename: D
authors.initials: D
authors.lastname: Gittings
authors.forename: J
authors.initials: J
authors.lastname: Colussi-Mas
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D006213:Hallucinogens; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine