Changes in the behavioural response to a TRH analogue following chronic amitriptyline treatment and repeated...

The arousal elicited in rats by injection into the nucleus accumbens of the thyrotrophin-releasing hormone analogue CG 3509 (orotyl-histidyl-prolineamide) was used to assess the responsiveness to thyrotrophin-releasing hormone following repeated treatment with amitriptyline or electroconvulsive shock. Fourteen day administration of amitriptyline (15 mg kg-1 i.p. twice daily) reduced the behavioural response to bilateral intra-accumbens injection of CG 3509 (2 X 2.5 micrograms). CG 3509-induced hyperactivity, recovery from pentobarbitone-induced anaesthesia and the reversal of both pentobarbitone-induced hypothermia and decreased respiration, were all significantly reduced compared to either the response of the animals prior to amitriptyline administration or that observed in rats following chronic saline administration. Repeated administration of electroconvulsive shock (5 shocks over 10 days) significantly increased CG 3509-induced hyperactivity and the degree of reversal of pentobarbitone-induced hypothermia and respiratory depression following CG 3509 administration. The results demonstrate that chronic antidepressant treatments alter the central functional responsiveness to thyrotrophin-releasing hormone. These changes are discussed with respect to the effects of antidepressant treatments on 5-hydroxytryptamine receptors and possible thyrotrophin-releasing hormone--aminergic interactions.