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


OBJECTIVE
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.


CONCLUSIONS
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.
Moreira
Fabrício Araújo
FA
Department of Pharmacology, FMRP, Campus USP, 14049-900 Ribeirão Preto, SP, Brazil.
Guimarães
Francisco Silveira
FS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D012054:Reinforcement, Psychology; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013238:Stereotaxic Techniques
D000662:Amphetamines; D018755:GABA Agonists; D018757:GABA Modulators; D020030:Nitric Oxide Donors; D044402:Receptor, Serotonin, 5-HT2A; D011963:Receptors, GABA-A; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; C002385:linsidomine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008981:Molsidomine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D008874:Midazolam