Different projection neurons of basolateral amygdala participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.

Context-induced retrieval of drug withdrawal memory is one of the important reasons for drug relapses. Previous studies have shown that different projection neurons in different brain regions or in the same brain region such as the basolateral amygdala (BLA) participate in context-induced retrieval of drug withdrawal memory. However, whether these different projection neurons participate in the retrieval of drug withdrawal memory with same or different molecular pathways remains a topic for research. The present results showed that (1) BLA neurons projecting to the prelimbic cortex (BLA-PrL) and BLA neurons projecting to the nucleus accumbens (BLA-NAc) participated in context-induced retrieval of morphine withdrawal memory; (2) there was an increase in the expression of Arc and pERK in BLA-NAc neurons, but not in BLA-PrL neurons during context-induced retrieval of morphine withdrawal memory; (3) pERK was the upstream molecule of Arc, whereas D1 receptor was the upstream molecule of pERK in BLA-NAc neurons during context-induced retrieval of morphine withdrawal memory; (4) D1 receptors also strengthened AMPA receptors, but not NMDA receptors, -mediated glutamatergic input to BLA-NAc neurons via pERK during context-induced retrieval of morphine withdrawal memory. These results suggest that different projection neurons of the BLA participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.

Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice.

The lateral hypothalamus (LH) is physiologically critical in brain functions. The LH also plays an important role in drug addiction. However, neural circuits underlying LH involvement of drug addiction remain obscure. In the present study,our results showed that in male mice, during context-induced expression of morphine withdrawal memory, LH glutamatergic neurons played an important role; dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) projecting from the core of nucleus accumbens (NAcC) to the LH were an important upstream circuit to activate LH glutamatergic neurons; D1-MSNs projecting from the NAcC to the LH activated LH glutamatergic neurons through inhibiting LH local gamma-aminobutyric acid (GABA) neurons. These results suggest that disinhibited LH glutamatergic neurons by neural circuits from the NAcC importantly contribute to context-induced the expression of morphine withdrawal memory.

Two kinds of transcription factors mediate chronic morphine-induced decrease in miR-105 in medial prefrontal cortex of rats.

Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.