The duration of withdrawal affects the muscarinic signaling in the nucleus accumbens after chronic morphine exposure in neonatal rats

Abstract

The infants experience withdrawal from opiates, and time-dependent adaptations in neuronal activity of nucleus accumbens (NAc) may be crucial for this process. A key adaptation is an increased release of acetylcholine. The present study investigates muscarinic acetylcholine receptors (mAChRs) functions in the NAc at short-term (SWT) and long-term withdrawal time (LWT) following chronic morphine exposure in neonatal rats. The inhibitory role of presynaptic mAChRs activation in spontaneous excitatory postsynaptic currents (sEPSCs) in medium spiny neurons was decreased at LWT but not at SWT. Whereas, the excitatory role of post/extrasynaptic mAChRs activation in membrane currents was reduced at LWT but enhanced at SWT. Furthermore, the inhibitory effect of acute morphine on post/extrasynaptic mAChRs-mediated inward currents was enhanced at SWT but not at LWT. These results suggest that withdrawal from morphine leads to downregulation of presynaptic and post/extrasynaptic mAChRs functions in the NAc, which may co-regulate the development of withdrawal in neonates.

Molecular Basis for Morphine Addiction

“…Behavioural and neurochemical changes due to morphine usage are influenced by the adaptation in the neurotransmission process. Chronic morphine usage induces the cholinergic signalling pathways by significantly altering the level of acetylcholine (ACh) (depending on the region of the brain) [70] while its acute treatment reduces [71] or has no effect on its level [72].…”