Regional differences in naloxone modulation of Delta(9)-THC induced Fos expression in rat brain

Recent behavioral and pharmacological research shows extensive interplay between cannabinoid and opioid neurochemical systems. Here we examined the neuroanatomical basis of this interaction using c-fos immunohistochemistry. We compared Fos immunoreactivity in groups of male albino Wistar rats treated with vehicle, Delta(9)-tetrahydrocannabinol (THC, 10 mg/kg, i.p.), naloxone (10 mg/kg, i.p.) or THC and naloxone in combination. Locomotor activity was depressed in both THC treatment groups and moderately inhibited in rats given naloxone alone. Results showed that naloxone inhibited THC-induced Fos immunoreactivity in several key brain regions including the ventral tegmental area, ventromedial and dorsomedial hypothalamus, central caudate-putamen and ventrolateral periaqueductal grey. Conversely, naloxone and THC had an additive effect on Fos immunoreactivity in the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division), the insular cortex, and the paraventricular nucleus of the thalamus. These findings complement earlier pharmacological results showing potent modulation of cannabinoid-induced analgesia, appetite and reward by opioids. The inhibitory effects of naloxone on THC-induced ventral tegmentum, hypothalamic and periaqueductal grey Fos expression point to these structures as key sites involved in cannabinoid-opioid interactions.