The current study assessed the ability of the selective irreversible μ-opioid receptor antagonists β-funaltrexamine (βFNA) and naloxonazine (NALZ) to alter the locomotor and rewarding effects of a single intravenous injection of morphine using the conditioned place preference (CPP) model. In the first experiment, rats were conditioned with a single injection of morphine (10 mg/kg iv) paired with one compartment of a CPP apparatus and then were tested for CPP at either 1 or 7 days after conditioning. Rats showed hypoactivity following acute morphine on the conditioning trial and showed CPP when tested either 1 or 7 days later. In the next experiments, rats were pretreated with βFNA (20 mg/kg sc, 20 h before conditioning), NALZ (15 or 30 mg/kg sc, 24 h before conditioning) or saline and then were conditioned with a single injection of morphine (10 mg/kg iv) or saline. Pretreatment with NALZ alone, but not βFNA, significantly decreased locomotor activity; neither antagonist alone produced a significant shift in preference for either compartment of the CPP apparatus. Pretreatment with either βFNA or NALZ blocked completely morphine-induced hypoactivity, but neither antagonist had a significant effect on morphine CPP. These results indicate that μ-opioid receptors are more critically involved in acute morphine-induced hypoactivity than in acute morphine reward.

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Bardo, M.T., B. J. Gehrke, B. E. Shortridge, and A.S. Rauhut. Effects of β-Funaltrexamine and Naloxonazine on Single-Trial Morphine-Conditioned Place Preference and Locomotor Activity. Pharmacology, Biochemistry, and Behavior 74, no. 3 (2003): 617-622. doi: 10.1016/S0091-3057(02)01049-3

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