Selective modulation of the PKCɛ/p38MAP kinase signalling pathway for the antidepressant-like activity of amitriptyline

► PKCɛ involvement in depression and in the antidepressant activity of amitriptyline. ► Blockade of p38MAPK signalling reduced immobility time in the forced swimming test. ► Antidepressant phenotype by inhibition of the PKCɛ/p38MAPK signalling cascade. ► Increased JNK phosphorylation as negative modulation of antidepressant properties.