Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine

DUSICA BAJIC; MARIANO SOIZA REILLY; ALLEGRA L. SPALDING; CHARLES B. BERDE; KATHRYN G. COMMONS

New Orleans

Congreso; 42nd Society for Neuroscience Annual Meeting; 2012

Society for Neuroscience

Neuroplasticity in the periaqueductal gray (PAG) is critical for behavioral adaptations following chronic morphine administration. We have used a molecular-based approach in a rat model to examine how chronic morphine changes gene expression in the PAG using Neurotransmitters and Receptors PCR array (SABiosciences, MD) that profiles the expression of 84 genes. We have analyzed: (1) control, injected with normal saline, and (2) chronic morphine group. Animals received either morphine (10 mg/kg) or equal volume of normal saline subcutaneously twice daily for 6.5 days. Tissue blocks containing ventral and ventrolateral PAG from different animals in the same group were processed together for total RNA isolation prior to PCR array processing (5 animals/group with 3 replicates). Analysis revealed that chronic morphine administration was associated selectively with significant changes in expression of genes associated with cholinergic neurotransmission. Furthermore, we characterized the functional importance of cholinergic neurotransmission on chronic morphine behavioral effects: antinociceptive tolerance, locomotor sensitization and dependence in the presence of nicotinic antagonist, mecamylamine (0.5 or 2 mg/kg). Chronic mecamylamine administration did not have any effect on acute morphine antinociceptive effects, antinociceptive tolerance, or dependence. We have found a clear dissociation of behavioral effects such that cholinergic neurotransmission contributes selectively to expression and development of locomotor sensitization in a dose-dependent manner. These data suggest that endogenous nicotinic cholinergic neurotransmission selectively participates in behavioral sensitization to morphine.