The mechanisms and sites of action of
epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the locus coeruleus is a site of action of
epibatidine. Behavioral responses of rats to hindpaw
formalin injection were compared after direct administration of
epibatidine into the locus coeruleus (LC), and after subcutaneous administration. Different groups of rats were injected with
formalin into the rear paw after administration of either ACSF,
epibatidine (0.01, 0.06, 0.12, and 0.3mug) into the locus coeruleus or
epibatidine (2.5-5mug/kg) subcutaneously. Assessment of
pain-related behavior was done by evaluating the incidence of favoring, lifting and licking of the injected paw in the different groups. Abnormal motor behavior was also recorded. Infusion of
epibatidine into LC induced
analgesia, which was reversed by prior infusion of
mecamylamine into LC.
Epibatidine into the locus coeruleus resulted in a significant lower
pain score in the second phase of the
formalin test compared to control rats and was as effective as subcutaneous
epibatidine. The
analgesic effects of
epibatidine were regionally selective in that the administration of
epibatidine outside the locus coeruleus area was not
analgesic. The every tested dose of
epibatidine administered into the locus coeruleus also produced freezing behavior immediately after injection, which was relatively short-lived compared to the
analgesic effect. Freezing was inhibited by administration of
mecamylamine into the LC. Together the results implicate the LC as a target for the
analgesic effects of
epibatidine.