title: Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.
abstract: Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg.
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, United States of America; Department of Anaesthesia, Harvard Medical School, 25 Shattuck St., Boston, MA, 02115, United States of America.
authors: Dusica
authors: D
authors: Bajic
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, United States of America; Department of Anaesthesia, Harvard Medical School, 25 Shattuck St., Boston, MA, 02115, United States of America.
authors: Mariano
authors: M
authors: Soiza-Reilly
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, United States of America.
authors: Allegra L
authors: AL
authors: Spalding
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, United States of America; Department of Anaesthesia, Harvard Medical School, 25 Shattuck St., Boston, MA, 02115, United States of America.
authors: Charles B
authors: CB
authors: Berde
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, United States of America; Department of Anaesthesia, Harvard Medical School, 25 Shattuck St., Boston, MA, 02115, United States of America.
authors: Kathryn G
authors: KG
authors: Commons
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000032:analysis / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D050494:Vesicular Acetylcholine Transport Proteins; D009020:Morphine
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