Down regulation of cerebral cortical 3H imipramine binding sites during chronic antidepressant treatment is independent of the central serotonergic innervation.
The effects of chronic antidepressant (AD) administration (amitryptiline 12 mg/Kg i.p., 20 days) on cerebral cortical [3H] imipramine binding sites were examined in control rats and in serotonergic denervated animals. Both treatments independently reduced the density of [3H] imipramine binding sites by 33-40%. Animals submitted to both treatments showed a slightly higher decrease in the Bmax (-50%). No alterations were observed in the apparent dissociation constant. Preincubation of cerebral cortical synaptosomal membranes with Triton X-100 (0.2% v/v), which preferentially dissolves the presynaptic component of the synaptosomes, reduced by 40% the maximal number of [3H] imipramine binding sites in control rats. In chronic AD treated rats or in serotonergic lesioned rats, membranes preincubated with Triton X-100 showed a 30% decrease in the number of [3H] imipramine sites in comparison to the sham group. The combination of both treatments produced an even larger decrease in the density of [3H] imipramine binding sites in Triton X-100 treated membranes (-55%) compared to the sham group. Taken together, these results strongly suggest that cerebral cortical [3H] imipramine binding sites located both pre- and postsynaptically, are down regulated by the long term AD administration independently of the integrity of the central serotonergic system.
Stockert
M
M
Instituto de Biología Celular, Facultad de Medicina, Buenos Aires, Argentina.
Silveira
R
R
Zieher
L M
LM
Dajas
F
F
Medina
J H
JH
D015116:5,7-Dihydroxytryptamine / Q000378:metabolism; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001679:Biogenic Amines / Q000032:analysis; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D007099:Imipramine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*
D001679:Biogenic Amines; D000639:Amitriptyline; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D007099:Imipramine