Dopamine D3 receptor ligands modulate the acquisition of morphine-conditioned place preference.
BACKGROUND
The dopamine D3 receptor has been shown to mediate conditioned effects of psychostimulants such as cocaine. The present work was aimed at determining whether drugs acting at D3 receptors alter acquisition of conditioned effects of opiates.


METHODS
We have used the conditioned place preference (CPP) in mice, which permits the measurement of approach behaviour to environmental stimuli previously paired with drug effects. To assess the interaction of morphine and D3 receptor ligands during acquisition of CPP, we have used a particular procedure, in which the animals were given the choice between compartments associated with either morphine alone or the combination of morphine with the tested agent.


RESULTS
D3 receptor agonists (7-OH-DPAT, quinelorane, BP 897) did not induce, alone, a significant CPP but, all of them, at the doses tested, and notably BP 897, a highly selective partial agonist, significantly enhanced acquisition of morphine-induced CPP when administered together with morphine at each conditioning session. PNU-99194A, a D3 receptor-preferring antagonist, induced a CPP itself at the dose of 10 mg/kg but not at 5 or 15 mg/kg and impaired significantly at 10 and 15 mg/kg the morphine-induced CPP. In contrast, BP 897 did not alter morphine-induced analgesia, an unconditioned effect of this drug.


CONCLUSIONS
These results suggest the stimulation of D3 receptors has no rewarding effect per se, but may synergize upon opiate-induced dopamine release with stimulation of other dopamine receptor subtypes to enhance approach behaviour to morphine-associated environment.
Francès
Henriette
H
Unité de Neurobiologie et Pharmacologie Moléculaire (INSERM U 573), Centre Paul Broca, 2ter, rue d'Alésia, 75014 Paris, France. frances@broca.inserm.fr
Smirnova
Maria
M
Leriche
Ludovic
L
Sokoloff
Pierre
P
D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493594:Drd3 protein, mouse; D008024:Ligands; D010879:Piperazines; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C120565:BP 897; D009020:Morphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin