Morphine self-administration alters the expression of translational machinery genes in the amygdala of male Lewis rats

Abstract

Background:
Addiction is a chronic disorder with a high risk of relapse. The neural mechanisms mediating addictions require protein synthesis, which could be relevant for the development of more effective treatments. The mTOR signaling pathway regulates protein synthesis processes that have recently been linked to the development of drug addiction.

Aims:
To assess the effects of morphine self-administration and its subsequent extinction on the expression of several genes that act in this pathway, and on the levels of specific phosphoproteins (Akt, Gsk3α/β, mTOR, PDK1 and p70 S6 kinase) in the amygdala, nucleus accumbens, and the prefrontal cortex.

Methods:
Male Lewis rats underwent morphine self-administration (1 mg/kg) for 19 days. They subsequently were submitted to extinction training for 15 days. Rats were killed either after self-administration or extinction, their brains extracted, and gene expression or phosphoprotein levels were assessed.

Results:
We found an increase in Raptor and Eif4ebp2 expression in the amygdala of rats that self-administered morphine, even after extinction. The expression of Insr in the amygdala of control animals decreased over time while the opposite effect was seen in the rats that self-administered morphine.