en Pain and addiction Neurophysiology/Pharmacology Experimental research article Experimental research article Background: Previous studies have confirm the effects of water extract of Crocus sativus on the euphoric and behavioral properties of morphine in mice. Objective: 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. Material and Methods: This experimental study was conducted on the 78 male rats that were divided in 18 groups (n=6/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 induction of 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 were tested in the animals. One-way Analysis of Variance (ANOVA) was proformed for statistical procedure. Results: Administration of morphine (0.5, 1, 5, 7.5 and 10 mg/kg), indcreased the time spend in the compartment paired with morphine (i.e. conditioned place preference-CPP). The increament was significant for the dose 10 mg/kg of morphine. 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. 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 in which reveived morphine (10 mg/kg) in the conditioning days decreased the expression of morphine CPP in the animals which was statisticaly significant for doses 5 and 10 µg/rat of the extract. Conclusion: It could be concluded that intra-accumbens shell compartment njection of the alcoholic extract of C sativus can inhibit the acquisition and expression of morphine-induced CPP and shift it to the aversive state in rats. . Morphine, Conditioned place preference, Rats, Saffron Extract 121 128 http://ppj.phypha.ir/browse.php?a_code=A-10-74-46&slc_lang=en&sid=1 Narges-al-sadat Mojabi 320031947532846004002 320031947532846004002 No Azad Islamic University Akram Eidi 320031947532846004003 320031947532846004003 No Azad Islamic University Mohammad Kamalinejad 320031947532846004004 320031947532846004004 No Shaheed Beheshti University of Medical Sciences Ali Khoshbaten 320031947532846004005 320031947532846004005 No Baqyiatallah (a.s.) University of medical Sciences Ali Noroozzadeh 320031947532846004006 320031947532846004006 No Baqyiatallah (a.s.) University of medical Sciences Hedayat Sahraei h.sahraei@bmsu.ac.ir 320031947532846004007 320031947532846004007 Yes Baqyiatallah (a.s.) University of medical Sciences Farial Khamseh 320031947532846004008 320031947532846004008 No Baqyiatallah (a.s.) University of medical Sciences Farzaneh Zighimat 320031947532846004009 320031947532846004009 No Baqyiatallah (a.s.) University of medical Sciences