Adenosinergic nature of antidepressant-induced antinociception in mice

Abstract

The antinociceptive activity of the antidepressant agents imipramine, maprotiline and amitriptyline and their interactions with morphine and aminophylline were evaluated using the acetic acid writhing test of mouse. All the antidepressants induced a dose-dependent antinociceptive activity with a rank of potency was amitriptyline > maprotiline > imipramine. Antinociception was blocked by the pretreatment with 10 mg/kg of aminophylline, suggesting an interaction of these agents with adenosine receptors, which may cause the release of adenosine at neuronal level and depression of neuronal activity by inhibition of neurotransmitter release. Isobolographic analysis demostrated that the simultaneous administration of imipramine or maprotiline plus morphine (10:1 and 4.5:1 respectively) produced a supra-additive interaction, but the combination of amitriptyline and morphine (1:1) resulted in simple additivity. These effects were not antagonized by 1 or 10 mg/kg of aminophylline. The interaction between morphine and antidepressants seems to be due to an upregulated neuronal activity (i.e. indirect antagonism of the effect of the tricyclic agents) which could be dependent on the pharmacological profile of antidepressants with respect to their inhibition of bioamines uptake. Since antinociception was induced by acute administration of antidepressants, this action seems to be independent of antidepressive properties, which are obtained only after chronical administration. © 1997 John Wiley & Sons, Ltd.