Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat

Kyle N Campion; Kimber A Saville; Michael M Morgan

doi:10.1111/ejn.13378

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Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat

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Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat

Kyle N Campion, Kimber A Saville and Michael M Morgan

The European journal of neuroscience, Vol.44(9), pp.2667-2672

11/2016

DOI: https://doi.org/10.1111/ejn.13378

Handle:

https://hdl.handle.net/2376/112811

PMCID: PMC5300757

PMID: 27564986

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Abstract

Nociception

Morphine - pharmacology

Drug Tolerance

Injections, Intraventricular

Periaqueductal Gray - drug effects

Analgesics, Opioid - pharmacology

Rats

Male

Rats, Sprague-Dawley

Animals

Raphe Nuclei - drug effects

Raphe Nuclei - physiology

Analgesics, Opioid - administration & dosage

Periaqueductal Gray - physiology

Morphine - administration & dosage

The dorsal raphe nucleus (DRN) is embedded in the ventral part of the caudal periaqueductal gray (PAG). Electrical or chemical activation of neurons throughout this region produces antinociception. The objective of this manuscript is to determine whether the ventrolateral PAG and DRN are distinct antinociceptive systems. This hypothesis was tested by determining the antinociceptive potency of microinjecting morphine into each structure (Experiment 1), creating a map of effective microinjection sites that produce antinociception (Experiment 2) and comparing the development of antinociceptive tolerance to repeated microinjections of morphine into the ventrolateral PAG and DRN (Experiment 3). Morphine was more potent following cumulative injections (1.0, 2.2, 4.6 & 10 μg/0.2 μL) into the ventrolateral PAG (D = 3.3 μg) compared to the lateral (4.3 μg) or medial DRN (5.8 μg). Antinociception occurred following 94% of the morphine injections into the ventrolateral PAG, whereas only 68.3% and 78.3% of the injections into the lateral and medial aspects of the DRN produced antinociception. Repeated microinjections of morphine into the ventrolateral PAG produced tolerance as indicated by a 528% difference in potency between morphine and saline pretreated rats. In contrast, relatively small changes in potency occurred following repeated microinjections of morphine into the lateral and medial aspects of the DRN (107% and 49%, respectively). These data indicate that the ventrolateral PAG and DRN are distinct antinociceptive structures. Antinociception is greater with injections into the ventrolateral PAG compared to the DRN, but this antinociception disappears rapidly because of the development of tolerance.

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Title: Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat
Creators: Kyle N Campion - Department of Psychology, Washington State University Vancouver, 14204 NE Salmon Creek Ave., Vancouver, WA, 98686-9600, USA
Kimber A Saville - Department of Psychology, Washington State University Vancouver, 14204 NE Salmon Creek Ave., Vancouver, WA, 98686-9600, USA
Michael M Morgan - Department of Psychology, Washington State University Vancouver, 14204 NE Salmon Creek Ave., Vancouver, WA, 98686-9600, USA. mmmorgan@wsu.edu
Publication Details: The European journal of neuroscience, Vol.44(9), pp.2667-2672
Academic Unit: Psychology, Department of
Publisher: France
Grant note: R01 DA015498 / NIDA NIH HHS
Identifiers: 99900547627401842
Language: English
Resource Type: Journal article