MODELING THE CHANGES INDUCED BY CHRONIC DESIPRAMINE TREATMENT ON THE FACTORS GOVERNING THE AGONISM AT PREJUNCTIONAL ALPHA(2)-ADRENOCEPTORS

1 The adaptational changes induced after chronic desipramine treatment on functional responsiveness of alpha(2)-adrenoceptor activation were investigated in prostatic portions of the rat vas deferens. 2 For thi s purpose, clonidine and xylazine were studied for their effects on tw itch contractions elicited by electrical field stimulation of prostati c portions removed 48 h after the last injection to the animals of veh icle or desipramine (10 mg kg(-1), i.p.; 14 days). Operational model-f itting and the nested hyperbolic method were used to analyse the effec ts of irreversible receptor alkylation by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ, 300 nM) on the alpha(2)-adrenoceptor-mediate d effects of clonidine, either in vehicle- or in desipramine-treated a nimals. 3 Treatment with desipramine decreased the potency (increased the EC(50)) Of clonidine and xylazine by about 12 and 9 fold respectiv ely. However, the treatment did not modify the maximal effect (alpha) elicited by either agonist. The estimates of apparent affinity for clo nidine did not depend on the method of calculation as the 'null' metho d and the 'operational' method gave similar answers. Estimates of tau values for both agonists revealed that chronic desipramine treatment r esulted in significant decreases in the efficacy of agonists. However, desipramine treatment was not associated with significant changes in the affinity constant for clonidine while for xylazine, the operationa l model provided a higher estimate of K-A (lower affinity) after desip ramine treatment. 4 The results indicate a large receptor reserve at p rejunctional alpha(2)-adrenoceptors which is modulated by chronic desi pramine treatment. 5 The comparison of results obtained after chronic desipramine exposure with those by using EEDQ suggests that chronic de sipramine treatment is not a useful experimental intervention for the purpose of estimating agonist affinities and efficacies.