Selective antagonism at dopamine D3 receptors attenuates cocaine-seeking behaviour in the rat.
Dopamine (DA) D3 receptors have been suggested to play a role in mechanisms underlying the ability of drug-associated cues to induce drug-seeking behaviour. The present study investigated whether SB-277011-A, a selective DA D3 receptor antagonist, modulates reinstatement of cocaine-seeking behaviour induced by cocaine-associated stimuli. The study also explored whether or not this modulation is generable to seeking behaviours associated with a nutritive reinforcer such as sucrose. Separate groups of rats were trained to associate discriminative stimuli (SD) with the availability of cocaine or sucrose pellets vs. non-reward under a FR1 schedule of reinforcement. Each reinforced response was followed by a response-cue signalling a 20-s time-out (TO). After the self-administration training criterion was met, rats underwent extinction during which cocaine, sucrose pellets and SDs were withheld. Reinstatement tests, separated by 3 d during which rates of responding under extinction conditions remained at the criterion, were performed by presenting SDs non-contingently together with the contingent presentation of response-cues signalling a 20-s TO. Within- and between-subjects experimental designs revealed that 10 and 30 mg/kg SB-277011-A attenuated reinstatement of cocaine-seeking. SB-277011-A (10 mg/kg) did not modify conditioned reinstatement triggered by sucrose pellet-associated cues. These results, provided they can be extrapolated to abstinent human addicts, suggest the potential therapeutic use of selective DA D3 receptor antagonists for the prevention of cue-controlled cocaine-seeking and relapse.
Cervo
Luigi
L
Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, Milan, Italy. cervo@marionegri.it
Cocco
Arianna
A
Petrella
Cinzia
C
Heidbreder
Christian A
CA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002405:Catheterization, Central Venous; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D012201:Reward; D055502:Secondary Prevention; D013395:Sucrose; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*
D018492:Dopamine Antagonists; D009570:Nitriles; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D013395:Sucrose