Brain region-specific studies of the excitatory behavioral effects of morphine-3-glucuronide

This study was designed to determine in rats whether morphine-3-glucuronide (M3G) produces its neuro-excitatory effects most potently in the ventral h ippocampus (as has been reported previously for subanalgesic doses of opioi d peptides). Guide cannulae were implanted into one of seven regions of the rat brain: lateral ventricle; ventral, CA1 and CA2-CA3 regions of the hipp ocampus; amygdala; striatum or cortex. After a 7 day recovery period, rats received intracerebral injections of (i) M3G (1.1 or 11 nmol) (ii) DADLE ([ D-Ala(2),D-Leu(5)]enkephalin), (45 nmol, positive controls) or (iii) vehicl e (deionised water), and behavioral excitation was quantified over 80 min. High-dose M3G (11 nmol) evoked behavioral excitation in all brain regions b ut the onset, severity and duration of these effects varied considerably am ong brain regions. By contrast, low-dose M3G (1.1 nmol) evoked excitatory b ehaviors only when administered into the ventral hippocampus and the amygda la, with the most potent effects being observed in the ventral hippocampus. Prior administration of the nonselective opioid antagonists, naloxone and beta-funaltrexamine into the ventral hippocampus, markedly attenuated low-d ose M3G's excitatory effects but did not significantly alter levels of exci tation evoked by high-dose M3G. Naloxone given 10 min after M3G (1.1 or 11 nmol) did not significantly attenuate behavioral excitation. Thus, M3G's ex citatory behavioral effects occur most potently in the ventral hippocampus as reported previously for subanalgesic doses of opioid peptides, and appea r to be mediated through at least two mechanisms, one possibly involving ex citatory opioid receptors and the other, non-opioid receptors.