Changes in the behavioural response to a TRH analogue following chronic amitriptyline treatment and repeated electroconvulsive shock in the rat

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Abstract
1 The arousal elicited in rats by injection into the nucelus 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. 2 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 × 2.5 μg). 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. 3 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. 4 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.