Study of the effects of intra-nucleus accumbens shell injections of alcohlic extract of Crocus sativus on the acquisition and expression of morphine-induced conditioned place preference in rats

Introduction: Previous studies have shown the effects of water extract of Crocus sativus on the euphoric and behavioral properties of morphine in mice. In the present study, the effects of intra-accumbal administration of alcohol extract of Crocus sativus stigma on the acquisition and expression of morphine-induced conditioned place preference (CPP) in male Wistar rats (250-300 g) were investigated. Methods: This study was conducted on 78 male rats that were divided in 13 groups (n = 6 each group). In a pilot study, different doses of morphine (0.5, 1, 2.5, 5, 7.5 and 10 mg/kg) were injected to the animals for evaluation of the drug's ability to induce place preference. In the second phase of the experiments, the extract of the C. sativus (1, 5 and 10 µg/rat), was administered into the nucleus accumbens shell during or after induction of morphine CPP. Then, CPP was tested in the animals. One-way Analysis of Variance (ANOVA) was preformed for statistical procedure. Results: Administration of morphine (0.5, 1, 5, 7.5 and 10 mg/kg), increased the time spent in the compartment paired with morphine (i.e. conditioned place preference-CPP) (P<0.05). This increase reached significance at the dose of 10 mg/kg. Injection of the same doses of the extract (1, 5 and 10 µg/rat) 5 min before morphine (10 mg/kg) administration, caused a decrease in the time spent in drug-paired side in doses 5 and 10 µg/rat of the extract (P < 0.0001). In addition, injection of the plant extract (1, 5 and 10 µg/rat) in to the shell part of nucleus accumbens in the test day to the animals that received morphine (10 mg/kg) in the conditioning days decreased the expression of morphine CPP in the animals. This effect was statistically significant for doses 5 and 10 µg/rat of the extract (P < 0.0001). Conclusion: It may be concluded that intra-accumbens shell compartment injection of the alcoholic extract of C sativus can inhibit the acquisition and expression of morphine-induced CPP and then shift it to the aversive state in rats.