Paradoxical effects after microinjection of morphine in the periaqueductal gray matter in the rat.

Paradoxical, concurrent hyper-and hyporeactivity of a profound nature to specific stimuli occurred when 10 micrograms of morphine was microinjected bilaterally into the periaqueductal gray matter of the rat brain. Both effects at this site were dose-dependent. The hyperreactivity (to previously neutral auditory and visual stimuli) was obtained only with intracerebrally injected morphine and never with intraperitoneally injected morphine or with other opiates administered either way. Rapid tolerance to toxic doses of morphine developed at this site, as well as cross tolerance of the hyporeactivity to painful stimuli between routes (intracerebral to intraperitoneal) of morphine administration. Both the hyper- and hyporeactivity were fully reversible by intracerebral injection of naloxone in the periaqueductal gray. Thus, the periaqueductal gray appears to be a major pathway for morphine action.