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OBJECTIVE To investigate the effect of injection of β2-adrenergic receptor agonist clenbuterol into the infralimbic cortex(IL) on drug-seeking behavior triggered by conditioned cues. METHODS Adult male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 d,followed by 2-h extinction training. Cue-induced heroin seeking was measured for 2 h. Clenbuterol was microinjected bilaterally into the IL(8 ng/side)of rats 15 min prior to reinstatement test. Meanwhile,locomotor activity was detected 15 min after clenbuterol or artifial cerebrospinal fluid(mod?el group) was microinjected bilaterally into IL. Western blotting was used to detect the expression of phosphorylated cyclic AMP response element-binding protein(p-CREB)in the prelimbic cortex(PL), IL,nucleus accumbens core (NACc) and shell (NACsh) of rats immediately after reinstatement test. RESULTS After heroin administration training for 14 consecutive days,these animals exhibited reliable heroin self-administration,indicated by the increase in active nose poke responses and infusions. The rats that had received infusion of clenbuterol into the IL had significantly lower active pokes (8 ± 3)than those in model group(45±10)in cue-induced reinstatement(P<0.01),but there was no significant differ?ence between clenbuterol group and vehicle group in the locomotor activity. The expression of p-CREB in either IL or NACsh was significantly decreased in clenbuterol group compared with model group(P<0.01,P<0.05),but significantly increased in NACc(P<0.01). CONCLUSION Microinjection of clenb?uterol into the IL can attenuate the cue-induced reinstatement of heroin-seeking behavior in rats. The underlying mechanism might be related to the regulation of p-CREB expression in the NACc and NACsh.
RESUMO
Objective To assess whether propofol call induce stable psychic dependence in the rats by self-administration experiment. Methods Twenty-four male SD rats 14 weeks old weighing 240一270 mg were studied. Anesthesia was performed with intraperitoneal injection of 3%sodium pentoharbitsl 40 ms/kg and atropine 03 mg/kg.A catheter wag inserted into the right external jugular vein. Penicillin(100 000 U)0.2 ml wag injected through the external jugular vein for anti-infection and heparin sodium(50U/ml)0.1 ml for anticoagulation. The self-administration experiment of 14 days was started after the 7 days of recovery. All the rats were randomly divided into 4 groups(n=6 each):contontrol group(C),propofol 0.56 mg/kg/l group(P1),propofol 1.00 mg/kg group(P2)and pmpofol 1.70 ms/kg group(P3).The experimental events were controlled by a computer with 50 times of the maximum injection per day.The times ofactive and inactive nose-poke response and times of drug iniection were recorded per day.Results Compared with group C and P1,the times of active nosepoke response and injections were significantly increased in group P2 and P3(P<0.01).The times of active nosepoke response and injections per day were significantly increased in group P3 than in group P2(P(0.01).There was no significant difference in the times of active nose-poke response and injections between group C and P1.There was no significant difference in inactive nose-poke resporme between the 4 groups.And the total daily doses of propofol injected in the last 3 days were significantly increased in a dose-dependent manner.Conclusion Propefol can induce the development of psychological dependence in rata and it is related to the dosage.