Effects of dopamine antagonists on drug cue-induced reinstatement of nicotine-seeking behavior in rats.
Dopaminergic neurotransmission has been implicated in associative learning processes related to drugs of abuse. However, it is not clear whether blockade of activation of dopamine receptors alters conditioned incentive properties of nicotine-associated cues. Using a response-reinstatement procedure, this study examined the effects of antagonists selective for the D1 and the D2 subtypes of dopamine receptors on cue-induced reinstatement of nicotine-seeking behavior. Male Sprague-Dawley rats were trained in 30 daily 1 h sessions to intravenously self-administer nicotine (0.03 mg/kg/infusion) on a fixed ratio 5 schedule and associate a conditioned stimulus (cue) with each nicotine delivery. After extinction of responding by withholding nicotine (saline substitution) and its cue, the reinstatement tests were conducted following subcutaneous administration of a D1 antagonist SCH23390 (0, 5, 10, 30 microg/kg) or a D2 antagonist eticlopride (0, 5, 10, 30 microg/kg) in different groups of animals. Both SCH23390 and eticlopride significantly attenuated the magnitude of cue-elicited reinstatement of nicotine-seeking responding. These results indicate that activation of dopaminergic D1 and D2 receptors may play a role in mediating the conditioned motivational effects of nicotine-associated cues as measured in the response-reinstatement procedure. These findings suggest that manipulation of dopaminergic neurotransmission at D1 and/or D2 receptors may prove to be a potential target for the development of pharmacotherapy for prevention of environmental nicotine cue-triggered smoking relapse.
Liu
Xiu
X
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. xliu@psychiatry.umsmed.edu
Jernigen
Courtney
C
Gharib
Maysa
M
Booth
Sheri
S
Caggiula
Anthony R
AR
Sved
Alan F
AF
D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control*; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology / Q000627:therapeutic use*; D055502:Secondary Prevention; D012646:Self Administration
D001552:Benzazepines; D018492:Dopamine Antagonists; C534628:SCH 23390; D012457:Salicylamides; D009538:Nicotine; C045989:eticlopride