Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis.

Single unit activity was recorded in the locus coeruleus (LC) of anesthetized, morphine-dependent rats during naltrexone-precipitated withdrawal. As has been reported previously, LC neurons displayed a strong withdrawal-induced activation of firing rate. Radio-frequency lesions of the nucleus paragigantocellularis (PGi), a major LC afferent, greatly attenuated withdrawal-induced activation of neurons in the LC ipsilateral but not contralateral to the PGi lesion. Lesions of the prepositus hypoglossi, another major LC afferent, did not prevent the withdrawal-induced activation of LC neurons. Kynurenic acid, a non-selective excitatory amino acid antagonist known to block PGi-induced excitations of LC neurons, also blocked the withdrawal-induced activation of LC neurons. These studies indicate that withdrawal-induced activation of the LC in opiate-dependent rats is mediated at least in part by afferents from the PGi which utilize an excitatory amino acid transmitter.