title: Effects of imipramine treatment on delta-opioid receptors of the rat brain cortex and striatum.
abstract: Imipramine (CAS 113-52-0) is being utilized widely for the treatment of major depression. In recent years, there has been evidence of the involvement of the endogenous opioid system in major depression and its treatment. There is some evidence indicating that opioid receptors could be involved in the antidepressant mechanism of action. Regarding this topic, mood-related behavior of endogenous enkephalins seems to be mediated by delta-opioid receptors. In this work, the effects of subacute (5 day) and chronic (15 day) treatments of imipramine on the density and the affinity of the delta-receptors in the striatum and in the parietal and frontal cortices of the rat brain are described. Studied parameters (Bmax and Kd) were calculated by a saturation binding assay with the delta-opioid agonists [3H]-DPDPE (tyrosyl-2,6-3H(N)-(2-D-penicillamine-5-D-penicillamine)-enkephalin) as specific ligand and DSLET ([D-serine2]-D-leucine-enkephalin-threonine) as non-radioactive competing ligand. It was found that 15 days treatment significantly decreased the delta-opioid receptor density,without changing the affinity, in the frontal cortex of the rat brain. That decrease was confirmed by delta-opioid receptor immunostaining. These results suggest that delta-opioid receptors could play a role in the chronic action mechanism of imipramine.
authors.affiliation: Department of Physiology, Medical School, University of the Basque Country, Bilbao, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Varona
authors.forename: Javier
authors.initials: J
authors.lastname: Gil
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Saracibar
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Maza
authors.forename: Enrique
authors.initials: E
authors.lastname: Echevarria
authors.forename: Jon
authors.initials: J
authors.lastname: Irazusta
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000378:metabolism / Q000493:pharmacokinetics; D007099:Imipramine / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D017465:Receptors, Opioid, delta; D020881:Enkephalin, D-Penicillamine (2,5)-; D007099:Imipramine