Chronic paroxetine increases [3H]nociceptin binding in rat dorsal raphe nucleus

Opioid-receptor-like I (ORLI) receptors, ORLI mRNA and nociceptin are particularly abundant in the limbic system and in central monoaminergic areas, brain regions involved in mood regulation and response to antidepressants. To analyse whether ORLI receptors adaptations occur during the first 3 weeks of an antidepressant treatment, we administered paroxetine to rats (10 mg/kg, i.p., once a day) for 4, 7,14 or 21 days. A significant increase (22-50%) in [3H]nociceptin binding sites density appeared specifically in the dorsal raphe nucleus after 4, 7 or 21 days of treatment, whereas no change was observed at any time in any other brain regions studied. These data constitute the first evidence of a modulation of ORLI receptors by an antidepressant treatment.