A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance

McCullough, Louise D.; Sokolowski, Jonathan D.; Salamone, John D.

doi:10.1016/0306-4522(93)90538-q

Cited by 170 publications

(113 citation statements)

References 28 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…In rat, 6-OHDA injection in the striatum led to increased operant escape failure in subjects exposed to IS, and the same effect was obtained when 6-OHDA was injected into the substantia nigra pars compacta (Winter et al, 2007). Also in rat, in the absence of prior IS, 6-OHDA NAcc DA depletion decreased operant (lever press) escape-avoid behaviour; furthermore, in intact subjects, performing this operant behaviour led to increased NAcc DA release (McCullough et al, 1993). Rats exposed to IS and exhibiting a high level of 2-way escape failure were characterised by a decrease in the proportion of active DA neurons in the VTA (Belujon and Grace, 2015).…”

Section: Discussionmentioning

confidence: 66%

“…As with positive stimuli, NAcc DA appears to modulate both the response-outcome learning and motivational aspects of behaviour relative to aversive stimuli. In rat, depletion of NAcc DA leads to a deficit in operant lever pressing or two-way shuttling to avoid-escape footshock (McCullough et al, 1993;Wenzel et al, 2015). In DA-deficient mice in which DA expression could be reactivated region-specifically, restoration of DA signalling to both entire striatum and amygdala was necessary and sufficient to enable mice to learn two-way active avoidance (Darvas et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies

et al. 2016

View full text Add to dashboard Cite

Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and deficient DA function could underlie motivational impairments in psychiatric disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for chronic DA depletion, principally applied in rat to study NAcc DA regulation of reward motivation. Given the increasing focus on studying environmental and genetic regulation of DA function in mouse models, it is important to establish the effects of 6-OHDA DA depletion in mice, in terms of reward and aversion processing. This mouse study investigated effects of 6-OHDAinduced NAcc DA depletion using the operant behavioural test battery of progressive ratio schedule (PRS), learned non-reward (LNR), learned helplessness (LH), treadmill, and in addition Pavlovian fear conditioning. 6-OHDA NAcc DA depletion, confirmed by ex vivo HPLC-ED, reduced operant responding: for gustatory reward under effortful conditions in the PRS test; to a stimulus recently associated with gustatory non-reward in the LNR test; to escape footshock recently experienced as uncontrollable in the LH test; and to avoid footshock by physical effort in the treadmill test. Evidence for specificity of effects to NAcc DA was provided by lack of effect of medial prefrontal cortex DA depletion in the LNR and LH tests. These findings add significantly to the evidence that NAcc DA is a major regulator of behavioural responding, particularly at the motivational level, to both reward and aversion. They demonstrate the suitability of mouse models for translational study of causation and reversal of pathophysiological DA function underlying motivation psychopathologies.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Acute exposure to aversive stimuli activates putative dopaminergic midbrain neurons and increases dopamine release in the accumbens (32). Additionally, rats trained to avoid footshock display elevated levels of extracellular dopamine in the accumbens during the instrumental response (33). This avoidance response was reportedly reduced by 6-hydroxy-dopamine lesions of the accumbens.…”

Section: Discussionmentioning

confidence: 99%

A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism

Kim

Pollak²,

Hjelmstad³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Repeated exposure to drugs of abuse produces forms of experience-dependent plasticity including behavioral sensitization. Although a single exposure to many addicting substances elicits locomotor sensitization, there is little information regarding the motivational effects of such single exposures. This study demonstrates that a single cocaine exposure enhances both rewarding and aversive forms of opioid place conditioning. Rats were given a single injection of cocaine (15 mg͞kg i.p.) in their home cage at different times before conditioning. This treatment enhanced conditioned place preference (CPP) to morphine (2 ؋ 10 mg͞kg s.c.) if training began 1 or 5 but not 10 days after the cocaine injection. A single cocaine exposure also enhanced conditioned place aversion (CPA) to the -opioid receptor agonist U69593 (2 ؋ 0.16 mg͞kg s.c.). Compared to morphine CPP, U69593 CPA was delayed and persistent. It was not observed at 1 day but appeared if the conditioning began 5 or 10 days after the cocaine injection. Although the cocaine-induced enhancements of both morphine CPP and U69593 CPA followed different time courses, suggesting different mechanisms, both effects were blocked by injection of the N-methyl-Daspartate receptor antagonist MK-801 (0.5 nmol bilaterally) into the ventral tegmental area, immediately before the cocaine injection. Thus, through a circuit involving the ventral tegmental area, a single cocaine exposure enhanced both -opioid receptor reward and -opioid receptor aversion.C hronic exposure to drugs of abuse produces enduring changes in neural circuits that underlie the addictive process. One consequence of this experience-dependent plasticity is a progressive increase in drug response on reexposure to the drug. Termed drug sensitization, the phenomenon is typically assessed as an enhancement in locomotor activity. Robust locomotor sensitization can be produced by psychostimulants (1), opiates (2), or ethanol (3), and cross-sensitization can occur between different drugs (4, 5).Whereas early studies of sensitization focused specifically on the progressive increase in locomotor activity (1), many researchers have since proposed that sensitization contributes to drug reward, and this process has been incorporated into several influential theoretical models of drug addiction. For example, sensitization processes have been proposed to contribute to impulsivity (6) or changes in incentive-salience state for cues associated with the drug (7). These proposals are supported by the observation that drug self-administration is enhanced after repeated drug administrations. For example, monkeys previously exposed to methamphetamine initiated self-administration to the stimulant at lower doses than drug-naïve subjects (8). Moreover, preexposure to amphetamine was sufficient to turn initial nonresponders into reliable self-administering rats (9). Finally, rats previously exposed to amphetamine exhibited higher break points than untreated rats to obtain the drug on a progressive ratio schedule of reinforcement (10...

show abstract

“…Other behavioral responses to aversive stimuli have been shown to activate midbrain dopaminergic neurons and increase dopamine release in the nucleus accumbens [27]. Similarly, nucleus accumbens dopamine was identified to be instrumental in an avoidance task to escape foot shock, and the avoidance task led to significant elevations of dopamine and dopamine metabolites within the nucleus accumbens, as measured by microdialysis [28]. Taken together, this data suggests that the involvement of nucleus accumbens dopamine is not unique to positively reinforced responses, but constitutes important motivational aversive behaviors that may contribute to the aversive emotional component of pain.…”

Section: Interplay Between Reward and Painmentioning

confidence: 98%

Migraine and Reward System—Or Is It Aversive?

Cahill¹,

Cook

Pickens

2014

Curr Pain Headache Rep

View full text Add to dashboard Cite

Migraine is a debilitating neurological disorder with grave consequences for both the individual and society. This review will focus on recent literature investigating how brain structures implicated in reward and aversion contribute to the genesis of migraine pain. There exist many overlapping and interacting brain regions within pain and reward circuitry that contribute to negative affect and subjective experience of pain. The emotional component of pain has been argued to be a greater metric of quality of life than its sensory component, and thus understanding the processes that influence this pain characteristic is essential to developing novel treatment strategies for mitigating migraine pain. We emphasize and provide evidence that abnormalities within the mesolimbic cortical reward pathways contribute to migraine pain and that there are structural and functional neuroplasticity within the overlapping brain regions common to both pain and reward.

show abstract

A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance

Cited by 170 publications

References 28 publications

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies

A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism

Migraine and Reward System—Or Is It Aversive?

Contact Info

Product

Resources

About