Strain-dependent neurochemical and neuroendocrine effects of desipramine, but not fluoxetine or imipramine, in Spontaneously Hypertensive and Wistar-Kyoto rats

Spontaneously Hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats differ i n their emotional responses to stress and antidepressant administration. We have analysed different neurochemical and psychoneuroendocrine responses t o repeated pretreatments with fluoxetine, imipramine or desipramine (10 mg/ kg p.o. daily for 4 weeks) in SHRs and WKY rats exposed to a daily 2-h rest raint episode for the last 5 days of antidepressant administration. Followi ng a 24-h wash-out period, WKY rats displayed higher plasma antidepressant and antidepressant metabolite levels than SHRs. Fluoxetine pretreatment dec reased [H-3]citalopram binding at midbrain serotonin (5-HT) transporters, w hereas tricyclic and/or fluoxetine decreased [H-3]ketanserin binding at cor tical 5-HT2A receptors, [H-3]CGP-12177 binding at cortical beta-adrenocepto rs, and [3H]nisoxetine binding at midbrain noradrenaline (NA) transporters in both strains. None of the antidepressants affected [H-3] 8-hydroxy-2-(di -N-propylamino)tetralin binding at hippocampal 5-HT1A receptors. In WKY rat s, repeated restraint triggered a desipramine-sensitive 140% increase in hy pothalamus [H-3]nisoxetine binding; moreover, plasma adrenocorticotropin-re leasing hormone responses to a 5-min open field test were amplified by prio r repeated restraint in both strains, but desipramine prevented such an amp lification in WKY rats only. However, neither elevated plus-maze nor open f ield behaviors of SHRs and WKY rats were affected by desipramine pretreatme nt. Thus, the SHR and WKY rat strains may prove useful in understanding how genetic differences in noradrenergic responses to repeated stress and desi pramine treatment impact on adaptive processes. (C) 2000 Elsevier Science L td. All rights reserved.