Single and repeated baclofen treatment attenuates the discriminative stimulus effects of morphine in rats

The GABAB agonists block the rewarding properties of opiates. However, the role of GABAB receptors in the discriminative properties of these drugs has received little attention. In this line, the present study was performed to investigate the effects of acute (Experiment 1) and chronic (Experiment 2) pretreatment with baclofen on the discriminative stimulus effects of morphine. Rats were trained to discriminate morphine (5 mg/kg i.p.) from saline under a two-lever fixed-ratio schedule of food reinforcement. Experiment 1: a morphine generalization curve was obtained under standard conditions in control and baclofen (1 and 2 mg/kg i.p.) pretreated animals. Acute baclofen pretreatment attenuated morphine-lever responding and response rate at both doses. Experiment 2: the animals were randomly divided in two groups and a morphine generalization curve was obtained in daily consecutive test sessions before (TEST1) and after (TEST2) chronic saline (Group I) or chronic baclofen (2 mg/kg) (Group II) administration. As expected, chronic saline pretreatment was ineffective, while chronic baclofen pretreatment attenuated the stimulus properties of morphine, without modifying the rate-decreasing effect of the drug.The data support a role for GABAergic neurotransmission in the discriminative effects of opiates and demonstrate that a short-term treatment with baclofen is useful for decreasing the sensitivity to narcotic cue.

Research Highlights
► Rats are trained to discriminate morphine from saline.
► Acute or chronic baclofen pre-treatment attenuates morphine stimulus properties.
► Acute, but not chronic, baclofen pre-treatment decreases response rate.
► Baclofen might be a promising medication for opiate addiction.