Abstract
Cholinergic stimulation of dopamine neurons in the ventral tegmental area (VTA) underlies
activation of the brain reward circuitry. Activation of this circuit is proposed to
preferentially suppress the affective reaction to noxious stimulation. Vocalization
afterdischarges (VADs) are a validated model of the affective response of rats to
noxious tail shock. The antinociceptive action of the acetylcholine agonist carbachol
microinjected into the VTA on VAD threshold was compared with its effect on the thresholds
of other tail shock–elicited responses (VDS, vocalizations during shock; SMR, spinal
motor reflexes). Whereas VADs are organized within the forebrain, VDSs and SMRs are
organized at medullary and spinal levels of the neuraxis, respectively. Carbachol
(1 μg, 2 μg, and 4 μg) injected into VTA produced dose-dependent increases in VAD
and VDS thresholds, although increases in VAD threshold were significantly greater
than increases in VDS threshold. Administration of carbachol into VTA failed to elevate
SMR threshold. Elevations in vocalization thresholds produced by intra-VTA carbachol
were reversed in a dose-dependent manner by local administration of the muscarinic
receptor antagonist atropine sulfate (30 μg and 60 μg). These results provide the
first demonstration of the involvement of the VTA in muscarinic-induced suppression
of pain affect.
Perspective
Cholinergic activation of the brain reward circuit produced a preferential suppression
of rats' affective reaction to noxious stimulation. The neurobiology that relates
reinforcement to suppression of pain affect may provide insights into new treatments
for pain and its associated affective disorders.
Key words
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Article info
Publication history
Published online: April 04, 2008
Accepted:
January 28,
2008
Received in revised form:
January 25,
2008
Received:
July 1,
2007
Footnotes
Supported by grant R01 NS045720 from the National Institute of Neurological Disorders and Stroke (NINDS) (to G.S.B.).
Identification
Copyright
© 2008 American Pain Society. Published by Elsevier Inc. All rights reserved.
