Effect of alprazolam on opiate withdrawal: a combined behavioural and microdialysis study

Benzodiazepines are commonly abused concurrently with opioids. The pharmacological rationale for this remains unknown. The present study has addressed behaviourally and neurochemically the action of alprazolam on the naloxone-precipitated morphine withdrawal syndrome in male rats. In naloxone (1 mg kg-1 i.p.)-precipitated morphine withdrawn rats, alprazolam (2.5 mg kg-1 s.c.) reduced the severity of the affective component, as measured by squeal on touch hostility, and the physical sequelae of opioid withdrawal. The microdialysis study in anaesthetized rats identified an increase in noradrenaline levels in hippocampal dialysates in rats undergoing naloxone-precipitated opioid withdrawal. Acute treatment with alprazolam (2.5 mg kg-1 s.c.) 20 min before administration of naloxone prevented the previously identified increase in noradrenaline in hippocampal dialysates. The only observable effect alprazolam induced in non-morphine-dependent rats was a 15% reduction in spontaneous locomotor activity. In conclusion, one interpretation of the data suggests that alprazolam decreases the withdrawal syndrome in rats through dampening down the previously identified hyperactivity of the locus coeruleus.