Noradrenergic transmission has been implicated in the affective component of relapse to tobacco smoking. Evidence in human and laboratory animals showed that smoking or nicotine administration may cause changes of the noradrenergic system resulting in hyperactivity in this system after cessation. The aim of the present work was to test the effects of the anti-adrenergic beta-blocker propranolol in a rat model of nicotine cue-induced relapse to verify the hypothesis that it may decrease affective activation and arousal observed during drug withdrawal or cue-induced relapse. We also tested the effects of propranolol on food cue-induced reinstatement of food-seeking on rats trained on food self-administration. Sprague Dawley rats were trained to lever press for food in Skinner box. After acquisition of responding, they underwent surgery for intravenous catheter implantation. After recovery, 1-sec i.v. nicotine (0.03 mg/kg) infusions (FR = 1, 3-hr session duration, 1 session/day; then on FR = 2) or 45 mg sugar pellet (FR = 2, TO = 60 s, session duration up to 25 reinforcers were delivered or 30 min) were available upon responding on active lever. Each nicotine infusion or 45-mg sugar pellet was contingent to 1-sec tone + green lamp + yellow lamp component (Cues). After 4 weeks (27 ± 1 self-administration sessions, means ± S.E.M.) on nicotine self-administration or 2 weeks on food self administration, saline substitution for nicotine - without Cues -, or the cessation of operant food delivery were the measures taken ¬in order to induce extinction of responding. When responding during the 1st hr was ≤ 50% of the 1st hr of extinction (19 ± 2 extinction sessions, 5 ± 0.2 extinction sessions for food), rats were re-exposed to Cues contingently upon responding for saline or for none rewards, in order to induce reinstatement (Relapse). Propranolol (1 or 10 mg/kg i.p.) or vehicle were given immediately prior to Relapse session to each rat. Propranolol transiently inhibited nicotine cue-induced reinstatement. The inhibitory effect of propranolol reached a peak after 30 min from the beginning of the reinstatement session, and then it declined up to a complete disappearance of effect at the end of the 3-h session. This inhibitory effect of propranolol was not observed when the drug was tested vs. reinstatement with food cues. The present study suggests a weak effect of propranolol to counteract nicotine cue-induced reinstatement of nicotine-seeking. Therefore, these findings do not support a potential use of propranolol for prevention of smoking relapse.
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