TY - JOUR

T1 - Real-Time Accumbal Dopamine Response to Negative Stimuli

T2 - Effects of Ethanol

AU - Mikhailova, Maria A.

AU - Deal, Alex L.

AU - Grinevich, Valentina P.

AU - Bonin, Keith D.

AU - Gainetdinov, Raul R.

AU - Budygin, Evgeny A.

PY - 2019

Y1 - 2019

N2 - Activity in the mesolimbic dopamine (DA) pathway is known to have a role in reward processing and related behaviors. The mesolimbic DA response to reward has been well-examined, while the response to aversive or negative stimuli has been studied to a lesser extent and produced inconclusive results. However, a brief increase in the DA concentration in terminals during nociceptive activation has become an established but not well-characterized phenomenon. Consequently, the interpretation of the significance of this neurochemical response is still elusive. The present study was designed to further explore these increases in subsecond DA dynamics triggered by negative stimuli using voltammetry in anesthetized rats. Our experiments revealed that repeated exposure to a tail pinch resulted in more efficacious DA release in rat nucleus accumbens. This fact may suggest a protective nature of immediate DA efflux. Furthermore, a sensitized DA response to a neutral stimulus, such as a touch, was discovered following several noxious pinches, while a touch applied before these pinches did not trigger DA release. Finally, it was found that the pinch-evoked DA efflux was significantly decreased by ethanol acutely administrated at an analgesic dose. Taken together, these results support the hypothesis that subsecond DA release in the nucleus accumbens may serve as an endogenous antinociceptive signal.

AB - Activity in the mesolimbic dopamine (DA) pathway is known to have a role in reward processing and related behaviors. The mesolimbic DA response to reward has been well-examined, while the response to aversive or negative stimuli has been studied to a lesser extent and produced inconclusive results. However, a brief increase in the DA concentration in terminals during nociceptive activation has become an established but not well-characterized phenomenon. Consequently, the interpretation of the significance of this neurochemical response is still elusive. The present study was designed to further explore these increases in subsecond DA dynamics triggered by negative stimuli using voltammetry in anesthetized rats. Our experiments revealed that repeated exposure to a tail pinch resulted in more efficacious DA release in rat nucleus accumbens. This fact may suggest a protective nature of immediate DA efflux. Furthermore, a sensitized DA response to a neutral stimulus, such as a touch, was discovered following several noxious pinches, while a touch applied before these pinches did not trigger DA release. Finally, it was found that the pinch-evoked DA efflux was significantly decreased by ethanol acutely administrated at an analgesic dose. Taken together, these results support the hypothesis that subsecond DA release in the nucleus accumbens may serve as an endogenous antinociceptive signal.

KW - dopamine

KW - ethanol

KW - nucleus accumbens

KW - pain

KW - Voltammetry

UR - http://www.scopus.com/inward/record.url?scp=85055184766&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/realtime-accumbal-dopamine-response-negative-stimuli-effects-ethanol

U2 - 10.1021/acschemneuro.8b00272

DO - 10.1021/acschemneuro.8b00272

M3 - Article

AN - SCOPUS:85055184766

VL - 10

SP - 1986

EP - 1991

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 4

ER -