Benzodiazepine receptor and serotonin 2A receptor modulate the aversive-like effects of nitric oxide in the dorsolateral periaqueductal gray of rats.

RATIONALE: Escape reactions induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) are inhibited by local administration of benzodiazepine (BZ) or serotonin (5-HT) receptor agonists. Nitric oxide (NO) is a gas messenger that may mediate aversive behaviors. NO donors injected into the dlPAG induce escape reactions.
OBJECTIVES: To test the hypothesis that the escape reactions induced by a NO donor in the dlPAG would be attenuated by pre-treatment with BZ-receptor or 5-HT-receptor agonists.
METHODS: Male Wistar rats with cannulae aimed at the dlPAG received microinjections of vehicle (0.2 microl), the BZ midazolam maleate (80 nmol), the 5-HT(1A)-receptor agonist 8-OH-DPAT (8 nmol or 16 nmol) or the 5-HT(2A/2C)-receptor agonist DOI (16 nmol) 10 min before the administration of the NO donor SIN-1 (150 nmol). Behavioral observation took place immediately after the last injection in an open arena over a 10-min period.
RESULTS: SIN-1 induced escape reactions characterized by running and jumps. Pre-treatment with DOI, but not 8-OH-DPAT, partially inhibited the effects of SIN-1. Pre-treatment with midazolam maleate, however, completely prevented the effects of the NO donor.
CONCLUSION: The results suggest that the aversive-like effects of NO donor in the dlPAG may be modulated by the BZ and 5-HT(2A/2C) receptors.