Dopamine D3 receptor ligands modulate the acquisition of morphine-conditioned place preference
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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.
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.
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.
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.
KeywordsDopamine D3 receptor Conditioned place preference BP 897 PNU-99194A 7-OH-DPAT Quinelorane Analgesia Mouse
- Arroyo M, Markou A, Robbins TW, Everitt BJ (1999) Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine. Neuropsychopharmacology 140:331–344Google Scholar
- Caine SB, Koob GF (1995) Pretreatment with the dopamine agonist 7-OH-DPAT shifts the cocaine self-administration dose-effect function to the left under different schedules in the rat. Behav Pharmacol 6:333–347Google Scholar
- Chaperon F, Thiébot MH (1996) Effects of dopaminergic D3 receptor-preferring ligands on the acquisition of place preference in rats. Behav Pharmacol 7:105–109Google Scholar
- Elmer GI, Pieper JO, Rubinstein M, Low MJ, Grandy DK, Wise RA (2002) Failure of intravenous morphine to serve as an effective instrumental reinforcer in dopamine D2 receptor knock-out mice. J Neurosci 15:RC224Google Scholar
- Khroyan TV, Fuchs RA, Baker DA, Neisewander JL (1997) Effects of D3-preferring agonists 7-OH-PIPAT and PD-128,907 on motor behaviors and place conditioning. Behav Pharmacol 8:65–74Google Scholar
- Kling-Petersen T, Ljung E, Svensson K (1995) Effects on locomotor activity after local application of D3 preferring compounds in discrete areas of the rat brain. J Neural Transm [Gen Sect] 102:209–220Google Scholar
- Pilla M, Hutcheson DM, Adib-Samil P, Everitt BJ (2001) Seeking responses for cocaine, heroin and natural reinforcers are differentially modulated by dopamine D3 receptors. Soc Neurosci Abstr 27:647.16Google Scholar
- Reavill C, Taylor SG, Wood MD, Ashmeade T, Austin NE, Avenell KY, Boyfield I, Branch CL, Cilia J, Coldwell MC, Hadley MS, Hunter AJ, Jeffrey P, Jewitt F, Johnson CN, Jones DNC, Medhurst AD, Middlemiss DN, Nash DJ, Riley GJ, Routledge C, Stemp G, Thewlis KM, Trail B, Vong AKK, Hagan JJ (2000) Pharmacological actions of a novel high-affinity, and selective human dopamine D3 receptor antagonist, SB-277011-A. J Pharmacol Exp Ther 294:1154–1165PubMedGoogle Scholar
- Waters N, Svensson K, Haadsma-Svensson SR, Smith MW, Carlsson A (1993) The dopamine D3 receptor: a postsynaptic receptor inhibitory on rat locomotor activity. J Neural Transm [Gen Sect] 94:11–19Google Scholar