Dopamine D3 receptor ligands show place conditioning effect but do not influence cocaine-induced place preference.
The importance of dopamine D3 receptors in reward related processes, especially in cocaine addiction, has been investigated extensively. However, in the reported studies a combination of different experimental conditions and different ligands have been used which renders the interpretation and comparison of the diverse results extremely difficult. Here, we report one comparative study investigating a wide range of dopamine D3 receptor ligands in one model of cocaine abuse: the place conditioning paradigm in rats. Of the antagonists tested, the moderately D3 selective nafadotride and the more selective SB-277011 did not produce any place conditioning effect while U-99194A caused place-preference. The most D3 selective agonist PD-128907, the less selective 7-OH-DPAT and the moderately selective partial agonist BP-897 all caused significant place aversion. None of the compounds influenced the cocaine-induced place preference. Results suggest the D3-preferring agonists could affect the reward mechanisms of the brain, however, modulation of D3 receptor function does not appear to be a significant mechanism for modifying the place conditioning effect of cocaine.
Gyertyán
István
I
Department of Behavioural Pharmacology, Gedeon Richter Ltd, Budapest, Hungary.
Gál
Krisztina
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology / Q000633:toxicity*; D003214:Conditioning, Classical / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D050637:Receptors, Dopamine D3; D012054:Reinforcement, Psychology; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000503:physiopathology*; D044005:Tetrahydroisoquinolines; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001552:Benzazepines; D001578:Benzopyrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D007189:Indans; D009281:Naphthalenes; D009570:Nitriles; D010078:Oxazines; D010879:Piperazines; D011759:Pyrrolidines; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; C120565:BP 897; D003042:Cocaine; D006220:Haloperidol; C097285:nafadotride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin