Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

“Cannulae were aimed at the caudal half of the accumbens: 2.8-2.2 mm anterior to bregma, 0.9 mm lateral to the midline, and 5.7 mm ventral to the skull surface (2.0 mm above the injection site), based on the atlas of Paxinos and Watson (1996).”

“For example, cocaine administration also activates CRF expression in CRH-producing neurons in hypothalamus and amygdala [13] and CRF given intracerebroventricularly (ICV) or into the ventrolateral BNST can induce reinstatement of drug self-administration behavior in the absence of external stressors (though this last…”

“The medial shell of nucleus accumbens also contains substantial distributions of CRF-immunoreactive and fibers, which might arise in part from hypothalamic CRF systems linked to stress, as well as cell bodies (particularly in its caudal half, and thus we focused on caudal shell here) [26].”

“Such appetitive behaviors have often been viewed as attempts to reduce or avoid unpleasant stress or as overflow from general motor arousal or frustration ([ 12-14 ] but see [8-11]).”

“Corticotropin-releasing factor (CRF) is involved in mediating the physiological and behavioral responses to stress [ 1-5 ].”

“Other neurochemical signals converging on the nucleus accumbens from mesocorticolimbic circuits could play roles in enhancing incentive salience too, either directly or by via dopamine modulation [18-20].”

“For example, 500 ng in the nucleus accumbens increased activation general behavioral activity counts, whereas 125 or 250 ng did not (and neither dose did when administered in lateral ventricles, consistent with an accumbens site of action) [ 32 ].”

“, cue-triggered 'wanting' for a reward, but not necessarily 'liking' for the same reward) has been shown to depend in part on ascending dopamine projections to nucleus accumbens [8-11].”

“Background Corticotropin-releasing factor (CRF) is involved in mediating the physiological and behavioral responses to stress [1-5].”

“Corticotropin-releasing factor (CRF) is involved in mediating the physiological and behavioral responses to stress [ 1-5 ].”

“, primary instrumental response reinforcement, secondary response reinforcement, discriminative stimulus occasion setting, general stress/frustration drive, Pavlovian S-R habits) [29-37].”

“Whether CRF acts directly on nucleus accumbens circuits in ways comparable to dopamine, or interacts with dopamine release in nucleus accumbens, CRF release in nucleus accumbens might facilitate incentive salience mechanisms [27-31].”

“Such appetitive behaviors have often been viewed as attempts to reduce or avoid unpleasant stress or as overflow from general motor arousal or frustration ([12-14] but see [8-11]).”

“For example, food intake and relapse into drug-taking in models of addiction are both increased by natural CRF-releasing stressors [ 6- 11 ].”

“Our procedure for measuring Fos plumes immediately surrounding a local microinjection site that are induced by drug was modified slightly from one previously described [43-45].”

“That seems consistent with demonstrations that HPA activation and glucocorticoid hormones may contribute to binge eating, drug addiction, and other excessive reward pursuits [22, 55 ].”

“Interaction is compatible with reports that, for instance, aversive stressors can cause dopamine release in nucleus accumbens (which has sometimes been used to argue against a purely positive motivational role of dopamine) [50,51].”

“that individuals try to counteract by pursuing and consuming hedonic rewards [21,47].”

“Nucleus accumbens contains levels of CRF receptors that are comparable to those in amygdala [ 23-25 ].”

“Thus, stress and glucocorticoids might 'energize' goal directed behaviors in part by activating CRF accumbens mechanisms that amplify the incentive salience of stimuli associated with reward [56,58].”

“Interaction is compatible with reports that, for instance, aversive stressors can cause dopamine release in nucleus accumbens (which has sometimes been used to argue against a purely positive motivational role of dopamine) [50,51].”

“Whether CRF acts directly on nucleus accumbens circuits in ways comparable to dopamine, or interacts with dopamine release in nucleus accumbens, CRF release in nucleus accumbens might facilitate incentive salience mechanisms [27-31].”

“Other neurochemical signals converging on the nucleus accumbens from mesocorticolimbic circuits could play roles in enhancing incentive salience too, either directly or by via dopamine modulation [18-20].”

“Our procedure for measuring Fos plumes immediately surrounding a local microinjection site that are induced by drug was modified slightly from one previously described [43-45].”

“Similar to previous PIT studies, we wished the CS- to serve as a control stimulus that was essentially irrelevant to reward and rewarded performance, rather than to suppress instrumental pressing as would either a novel stimulus or a strongly negative stimulus that was extensively paired with reward omission [ 59 ].”

“Regardless of the role of dopamine per se in stress, CRF might interact with mesolimbic mechanisms of incentive salience in nucleus accumbens either directly or by modulating dopaminerelated and/or glutamate-related signals [52].”

“For example, cocaine administration also activates CRF expression in CRH-producing neurons in hypothalamus and amygdala [13] and CRF given intracerebroventricularly (ICV) or into the ventrolateral BNST can induce reinstatement of drug self-administration behavior in the absence of external stressors (though this last…”

“Whether CRF acts directly on nucleus accumbens circuits in ways comparable to dopamine, or interacts with dopamine release in nucleus accumbens, CRF release in nucleus accumbens might facilitate incentive salience mechanisms [ 27-31 ].”

“that individuals try to counteract by pursuing and consuming hedonic rewards [21,47].”

“For example, CRF release is increased in the central nucleus of the amygdala by spontaneous food ingestion [10, 15 ] and in prefrontal cortex by presentation of Pavlovian cues associated with food reward [10].”

“Similarly, approach suppression indicates that CRF did not potentiate discriminative instrumental responding (in which the CS+ might have acted as a discriminative stimulus (SD) to signal that instrumental approach would be reinforced, and this instrumental relation might later have been generalized to lever pressing…”

“Glucocorticoids actually increase CRF expression in structures such as amygdala and BNST, and conceivably in accumbens shell too [ 56 ,57].”

“Glucocorticoids actually increase CRF expression in structures such as amygdala and BNST, and conceivably in accumbens shell too [56, 57 ].”

“For example, food intake and relapse into drug-taking in models of addiction are both increased by natural CRF-releasing stressors [ 6- 11 ].”

“Other neurochemical signals converging on the nucleus accumbens from mesocorticolimbic circuits could play roles in enhancing incentive salience too, either directly or by via dopamine modulation [18-20].”

“Nucleus accumbens contains levels of CRF receptors that are comparable to those in amygdala [23-25].”

“Similarly, sucrose ingestion normalizes CRF levels in hypothalamus and amygdala in adrenalectomized rats [ 16 ].”

“It excludes nonincentive explanations related to stress or stress reduction as well as other alternative explanations for increased behavior (e.g., primary instrumental response reinforcement, secondary response reinforcement, discriminative stimulus occasion setting, general stress/frustration drive, Pavlovian S-R ha…”

“Nucleus accumbens contains levels of CRF receptors that are comparable to those in amygdala [ 23-25 ].”

“Whether CRF acts directly on nucleus accumbens circuits in ways comparable to dopamine, or interacts with dopamine release in nucleus accumbens, CRF release in nucleus accumbens might facilitate incentive salience mechanisms [27-31].”

“Whether CRF acts directly on nucleus accumbens circuits in ways comparable to dopamine, or interacts with dopamine release in nucleus accumbens, CRF release in nucleus accumbens might facilitate incentive salience mechanisms [27-31].”

“Motor arousal and aversive effects can be caused by intracerebral microinjections CRF [38-40].”

“Similarly, CRF delivered to hypothalamus and amygdala may produce predominantly aversive effects, which typically suppress appetitive behaviors such as normal food intake [ 54 ].”

“Motor arousal and aversive effects can be caused by intracerebral microinjections CRF [38-40].”

“CRF 250 and 500 ng doses were chosen because they have previously been found to produce grooming, sniffing and oral motor behavioral effects when microinjected in nucleus accumbens shell [ 48 ].”

“, cue-triggered 'wanting' for a reward, but not necessarily 'liking' for the same reward) has been shown to depend in part on ascending dopamine projections to nucleus accumbens [8-11].”

“Motor arousal and aversive effects can be caused by intracerebral microinjections CRF [ 38-40 ].”

“, cue-triggered 'wanting' for a reward, but not necessarily 'liking' for the same reward) has been shown to depend in part on ascending dopamine projections to nucleus accumbens [8-11].”

“For example, the CRF-1 antagonist CP-154,526 has been reported to increase cocaine-associated dopamine release, at least in rostral shell of nucleus accumbens and pre-frontal cortex [53], and so any speculation about the potential relation of CRF antagonists to incentive salience must await future empirical investigat…”