AN EXAMINATION OF THE CENTRAL SITES OF ACTION OF CANNABINOID-INDUCED ANTINOCICEPTION IN THE RAT

Microinjections of low doses of the potent and selective cannabinoids WIN 55,212-2 and CP 55,940 into the lateral ventricle produce long-las ting reduction in sensitivity to noxious thermal stimuli (1). To deter mine the central distribution of ventricularly administered WIN55,212- 2, we microinjected an analgesic dose of the drug with [H-3]WIN55,212- 2. At the peak time of antinociception, the radiolabeled drug was conf ined to periventricular sites throughout the brain. The contribution o f particular periventricular structures to the antinociceptive effect was evaluated using intracerebral microinjection techniques and the ta il-flick test. Guide cannulae were implanted above the following periv entricular structures: the medial septal area, lateral habenlua, perih ypothalamic area, arcuate nucleus of the hypothalamus, dorsal raphe nu cleus and the dorsolateral and ventrolateral aspects of the periaquedu ctal gray. Microinjections of WIN55,212-2 (5 mu g/0.5 mu l) into the m edial septal area, lateral habenula, perihypothalamic area, arcuate nu cleus, and ventrolateral periaqueductal gray did not significantly aff ect tail-flick latencies. By contrast, microinjections of WIN55,212-2 into the dorsolateral periaqueductal gray and the dorsal raphe signifi cantly elevated tail-flick latencies. The results of this study indica te that at least two periventricular structures within the brain are i nvolved in cannabinoid antinociception.