Acute and chronic effects of desipramine and clorgyline on α2-adrenoceptors regulating noradrenergic transmission in the rat brain: a dual-probe microdialysis study

摘要

class="enumerated" style="list-style-type:decimal">The effects of desipramine (3 mg kg⁻¹ i.p.) and clorgyline (1 mg kg⁻¹ i.p.) on extracellular noradrenaline (NA) in the locus coeruleus (LC) and cingulate cortex were assessed in freely-moving rats by dual-probe microdialysis. Functional activities of α2-adrenoceptors regulating NA release in the LC and cingulate cortex were determined by systemic (0.3 mg kg⁻¹ i.p.) or local (0.1–100 μM) clonidine administration.Extracellular NA was increased in the LC and cingulate cortex following acute desipramine but not clorgyline treatment. Systemic clonidine decreased NA similarly in desipramine-, clorgyline-, and saline-treated animals, in both brain areas.Long-term (twice daily, 14 days) but not short-term (twice daily, 7 days) desipramine, and long-term clorgyline (once daily, 21 days) treatments increased NA (3 fold) in cingulate cortex but not in the LC. Following long-term treatments, responses of NA to systemic clonidine were attenuated in the LC and cingulate cortex.Clonidine perfusion by reverse dialysis into the cingulate cortex decreased local NA (−55±9%). The effect was attenuated by long-term desipramine (−31±9%) and clorgyline (−10±2%) treatments.Clonidine perfusion by reverse dialysis into the LC decreased NA in the LC (−89±2%) and in cingulate cortex (−52±12%). This effect was attenuated in the LC following long-term desipramine (−72±4%) and clorgyline (−62±12%) treatments but it was not modified in the cingulate cortex (−57±10% and −68±6%, respectively).These findings demonstrate that chronic desipramine or clorgyline treatments increase NA in noradrenergic terminal areas and desensitize α2-adrenoceptors modulating local NA release at somatodendritic and terminal levels. However, somatodendritic α2-adrenoceptors that control LC firing activity are not desensitized.