Abstract
The glutamate receptor subtype that mediates the morphine withdrawal–induced activation of locus coeruleus (LC) neurons was examined in this study using in vitro and in vivo single-unit electrophysiologic recordings. For LC neurons recorded in vitro in rat brain slices, the selective α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonist, LY293558, showed a greater than 10-fold selectivity for inhibiting the excitatory effects of AMPA vs kainate, and a greater than 30-fold selectivity for inhibiting the excitatory effects of AMPA vs NMDA.
LY293558 also greatly reduced the response of LC neurons to glutamate in a concentration-dependent manner. In in vivo recordings in anesthetized rats, pretreatment with LY293558 (0.1 to 10 mg/kg, IP) dose dependently suppressed the morphine withdrawal–induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY293558 (1 to 30 mg/kg, IP) dose dependently suppressed naltrexone-precipitated morphine withdrawal signs. These results indicate: (1) AMPA receptors mediate a large component of the excitatory effects of glutamate on LC neurons; (2) activation of AMPA receptors plays an important role in the morphine withdrawal–induced activation of LC neurons; (3) AMPA antagonists can suppress many signs of morphine withdrawal in awake animals; and (4) AMPA antagonists may have therapeutic effects in humans for the treatment of opiate withdrawal. © 1996 American College of Neuropsychopharmacology
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Rasmussen, K., Kendrick, W., Kogan, J. et al. A Selective AMPA Antagonist, LY293558, Suppresses Morphine Withdrawal-Induced Activation of Locus Coeruleus Neurons and Behavioral Signs of Morphine Withdrawal. Neuropsychopharmacol 15, 497–505 (1996). https://doi.org/10.1016/S0893-133X(96)00094-2
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DOI: https://doi.org/10.1016/S0893-133X(96)00094-2
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