Antinociception elicited by aversive stimulation of the inferior colliculus

We have shown that the inferior colliculus is involved in the integration of defensive reactions. Electrical and chemical stimulation of this structure elicits fear and escape behavior, expressed respectively by immobility (freezing) and wild running, followed by jumps. In this study, we analyzed whether the defensive behavior integrated at this level of the midbrain tectum is also followed by antinociception and its chemical mediation. In addition, we further addressed whether or not the aversive states and the stress-induced analgesia share the same neural substrates in the inferior colliculus. To this end, animals chronically implanted with a chemitrode, an electrode glued to a guide cannula, in the inferior colliculus were injected with naltrexone, methysergide, ketanserin, and midazolam. The animals were submitted to gradual increases in the electrical stimulation of the inferior colliculus, which allowed the measurement of the thresholds for aversive responses--vigilance, freezing, and escape. Following the induction of the aversive behavioral responses the animals were submitted to the tail-flick test. The results obtained show that midazolam was the only treatment that changed the aversive thresholds. On the other hand, while naltrexone and midazolam did not affect the fear-induced analgesia, it was inhibited by microinjections of the serotonergic blockers, methysergide and ketanserin. These results emphasize previous data demonstrating the nonopioid nature of the unconditioned analgesia to brain-aversive stimulation. Because methysergide is a nonspecific antagonist of 5-HT receptors, and ketanserin acts with a high degree of specificity at 5-HT2/5-HT1C receptors, the present results suggest that activation of 5-HT2/5-HT1C receptors may be implicated in the antinociception induced by stimulation of the inferior colliculus. Moreover, the present data also indicate that aversive reactions and analgesia from inferior colliculus stimulation can be pharmacologically dissociated.