Evolving concepts on the interactions between antidepressant treatments and monoamine neurotransmitters.

Most research on the mechanism of action of antidepressant drugs and repeated electroconvulsive shock (ECS) has focussed on changes in monoamine chemistry and function. Most antidepressant treatments, on repeated administration, decrease the number of beta-adrenoceptors in the cortex, a change which does not occur if 5-HT pathways to the cortex are lesioned, suggesting that 5-HT neurones play a permissive role in the change and high-lighting the complex neurotransmitter interactions that are present. Several drugs and electroconvulsive shock also attenuate the function of alpha 2-adrenoceptors (shown both by the sedation response and change in MOPEG-SO4 that occurs after injection of clonodine). Repeated treatment with the majority of antidepressant drugs decreases the number of 5-HT2 receptor and function. However, repeated electroconvulsive shock increases both these parameters. In contrast the hypothermic response which follows injection of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin-(8-OHDPAT) is attenuated not only after a range of diverse antidepressant drugs but also electroconvulsive shock. This suggests that the 5HT1A receptor is subsensitive after both antidepressant drugs and electroconvulsive shock. Recently, it has been demonstrated that a wide range of antidepressant drugs and electroconvulsive shock lead, on repeated administration, to an increase in the number of GABAB receptors and the enhancement of the degree of inhibition of release of 5-HT in cortical slices by the GABAB agonist baclofen suggests that a functional correlate of this change can be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)