Electroconvulsive therapy and the alpha-2 noradrenergic receptor: implications of treatment schedule effects

Six factorially designed studies evaluated the effects of different schedules of electroconvulsive shocks (ECSs) on alpha-2 adrenoceptor function in the rat brain. Attenuation of the hypomotility response to a clonidine challenge was taken to indicate alpha-2 adrenoceptor downregulation, a putative mediator of antidepressant action. Six daily and six alternate-day ECSs were shown separately to produce this receptor change. Three alternate-day ECSs produced comparable downregulation for a comparable period as six daily ECSs; this suggests that ECS produces time-dependent effects. No changes were elicited with a single ECS, which indicates that a single ECS may not influence alpha-2 receptor function. Three daily ECSs produced brief downregulation, which has implications for receptor dynamics as a function of the ECS schedule. Finally, maintenance ECSs sustained alpha-2 adrenoceptor downregulation over 6 weeks, which suggests a possible neurochemical basis for maintenance electroconvulsive therapy. The clinical relevance and scope for further research are discussed.