The dorsal raphe nucleus as a site of action of the antinociceptive and behavioral effects of the α4 nicotinic receptor agonist epibatidine

Giovanni Cucchiaro, Nayla Chaijale, Kathryn G. Commons

Research output: Contribution to journalArticle

Abstract

The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the dorsal raphe and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either epibatidine (0.01, 0.015, 0.03, and 0.06 μg) in the dorsal raphe or epibatidine (2.5-5 μg/kg) subcutaneously. Assessment of pain related behavior was done evaluating the incidence of favoring, lifting, and licking of the injected paw in the different groups. Abnormal behavior (freezing) was also recorded. Epibatidine was at least 100 times more potent when administered into the dorsal raphe nucleus versus systemically, implicating this nucleus as a site of action of the analgesic effects of epibatidine. Thus, epibatidine (0.015, 0.03, and 0.06 μg) in the dorsal raphe resulted in a significant lower pain score in the second phase of the formalin test compared with control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that administration of epibatidine within the periaqueductal gray area but outside the dorsal raphe area was not analgesic. The highest doses of intraraphe epibatidine (i.e., 0.03-0.06 μg) also produced "freezing" behavior immediately after injection, which was relatively short-lived compared with the analgesic effect. Together, the results implicate the dorsal raphe nucleus as a target for the analgesic and perhaps anxiogenic effects of epibatidine.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume313
Issue number1
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Fingerprint

epibatidine
Nicotinic Agonists
Nicotinic Receptors
Analgesics
Pain Measurement
Dorsal Raphe Nucleus
Formaldehyde
Freezing

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{f42640ee0f674d7a8eada8a5de6ec3ba,
title = "The dorsal raphe nucleus as a site of action of the antinociceptive and behavioral effects of the α4 nicotinic receptor agonist epibatidine",
abstract = "The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the dorsal raphe and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either epibatidine (0.01, 0.015, 0.03, and 0.06 μg) in the dorsal raphe or epibatidine (2.5-5 μg/kg) subcutaneously. Assessment of pain related behavior was done evaluating the incidence of favoring, lifting, and licking of the injected paw in the different groups. Abnormal behavior (freezing) was also recorded. Epibatidine was at least 100 times more potent when administered into the dorsal raphe nucleus versus systemically, implicating this nucleus as a site of action of the analgesic effects of epibatidine. Thus, epibatidine (0.015, 0.03, and 0.06 μg) in the dorsal raphe resulted in a significant lower pain score in the second phase of the formalin test compared with control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that administration of epibatidine within the periaqueductal gray area but outside the dorsal raphe area was not analgesic. The highest doses of intraraphe epibatidine (i.e., 0.03-0.06 μg) also produced {"}freezing{"} behavior immediately after injection, which was relatively short-lived compared with the analgesic effect. Together, the results implicate the dorsal raphe nucleus as a target for the analgesic and perhaps anxiogenic effects of epibatidine.",
author = "Giovanni Cucchiaro and Nayla Chaijale and Commons, {Kathryn G.}",
year = "2005",
month = "4",
day = "1",
doi = "10.1124/jpet.104.079368",
language = "English (US)",
volume = "313",
pages = "389--394",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - The dorsal raphe nucleus as a site of action of the antinociceptive and behavioral effects of the α4 nicotinic receptor agonist epibatidine

AU - Cucchiaro, Giovanni

AU - Chaijale, Nayla

AU - Commons, Kathryn G.

PY - 2005/4/1

Y1 - 2005/4/1

N2 - The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the dorsal raphe and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either epibatidine (0.01, 0.015, 0.03, and 0.06 μg) in the dorsal raphe or epibatidine (2.5-5 μg/kg) subcutaneously. Assessment of pain related behavior was done evaluating the incidence of favoring, lifting, and licking of the injected paw in the different groups. Abnormal behavior (freezing) was also recorded. Epibatidine was at least 100 times more potent when administered into the dorsal raphe nucleus versus systemically, implicating this nucleus as a site of action of the analgesic effects of epibatidine. Thus, epibatidine (0.015, 0.03, and 0.06 μg) in the dorsal raphe resulted in a significant lower pain score in the second phase of the formalin test compared with control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that administration of epibatidine within the periaqueductal gray area but outside the dorsal raphe area was not analgesic. The highest doses of intraraphe epibatidine (i.e., 0.03-0.06 μg) also produced "freezing" behavior immediately after injection, which was relatively short-lived compared with the analgesic effect. Together, the results implicate the dorsal raphe nucleus as a target for the analgesic and perhaps anxiogenic effects of epibatidine.

AB - The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the dorsal raphe and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either epibatidine (0.01, 0.015, 0.03, and 0.06 μg) in the dorsal raphe or epibatidine (2.5-5 μg/kg) subcutaneously. Assessment of pain related behavior was done evaluating the incidence of favoring, lifting, and licking of the injected paw in the different groups. Abnormal behavior (freezing) was also recorded. Epibatidine was at least 100 times more potent when administered into the dorsal raphe nucleus versus systemically, implicating this nucleus as a site of action of the analgesic effects of epibatidine. Thus, epibatidine (0.015, 0.03, and 0.06 μg) in the dorsal raphe resulted in a significant lower pain score in the second phase of the formalin test compared with control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that administration of epibatidine within the periaqueductal gray area but outside the dorsal raphe area was not analgesic. The highest doses of intraraphe epibatidine (i.e., 0.03-0.06 μg) also produced "freezing" behavior immediately after injection, which was relatively short-lived compared with the analgesic effect. Together, the results implicate the dorsal raphe nucleus as a target for the analgesic and perhaps anxiogenic effects of epibatidine.

UR - http://www.scopus.com/inward/record.url?scp=15744403996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15744403996&partnerID=8YFLogxK

U2 - 10.1124/jpet.104.079368

DO - 10.1124/jpet.104.079368

M3 - Article

C2 - 15608080

AN - SCOPUS:15744403996

VL - 313

SP - 389

EP - 394

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -