A LATERALIZED DEFICIT IN MORPHINE ANTINOCICEPTION AFTER UNILATERAL INACTIVATION OF THE CENTRAL AMYGDALA

The amygdala is a forebrain region that is receiving increasing attent ion as a modulator of pain sensation. The amygdala contributes to anti nociception elicited by both psychological factors (e.g., fear) and ex ogenous opioid agonists. Unlike the midbrain periaqueductal gray matte r (PAG) or rostral ventromedial medulla, the amygdala is a pain-modula ting region that has clear bilateral representation in the brain, maki ng it possible to determine whether pain-modulating effects of this re gion are lateralized with respect to the peripheral origin of noxious stimulation. Unilateral inactivation of the central nucleus of the amy gdala (Ce) plus adjacent portions of the basolateral amygdaloid comple x (with either the excitotoxin NMDA or the GABA(A) agonist muscimol) r educed the ability of morphine to suppress prolonged, formalin-induced pain derived from the hindpaw ipsilateral, but not contralateral, to the inactivated region. This effect was evident regardless of the noci ceptive scoring method used (weighted scores or flinch-frequency metho d) and was not accompanied by a concurrent reduction in morphine-induc ed hyperlocomotion. Unilateral lesions restricted to the basolateral a mygdaloid complex (i.e., not including the Ce) did not reduce the abil ity of morphine to suppress formalin-induced pain derived from either hindpaw. The results constitute the first report of a lateralized defi cit in opioid antinociception after unilateral inactivation of a speci fic brain area and show the first clear neuroanatomical dissociation b etween antinociceptive and motor effects of systemically administered morphine in the rat. The amygdala appears to modulate nociceptive sign als entering the ipsilateral spinal dorsal horn, probably through mono synaptic connections with ipsilateral portions of the PAG.