Opiate Withdrawal Induces Narp in the Extended Amygdala

Reti, Irving M.; Baraban, Jay M.

doi:10.1038/sj.npp.1300205

Cited by 25 publications

(29 citation statements)

References 31 publications

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“…After preconditioning, HR and LR animals were randomly assigned to one of the following treatment groups: NTX 1, 0.5, or 0.1 mg/kg. The dose of 1 mg/kg is the highest dose found in literature for systemic administration of NTX to induce withdrawal in morphine-dependent rats and it produces a severe withdrawal syndrome (Reti and Baraban, 2003;Aston-Jones et al, 1999;Delfs et al, 2000). Therefore, higher doses were not tested.…”

Section: Experiments Iii: Measurement Of Place Aversionmentioning

confidence: 99%

β1 Adrenergic Receptors in the Bed Nucleus of Stria Terminalis Mediate Differential Responses to Opiate Withdrawal

Cecchi

Capriles

Watson

et al. 2006

Neuropsychopharmacol

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The negative physical and affective aspects of opioid abstinence contribute to the prolongation of substance abuse. Withdrawal treatment is successful only in a subset of subjects, yet little is known about the neurobiological causes of these individual differences. Here, we compare the somatic and motivational components of opioid withdrawal in animals with high reactivity (HR) vs low reactivity (LR) to novelty, a phenotype associated with differential vulnerability to drug abuse. During withdrawal, HR relative to LR showed increased teeth chattering and eye twitching episodes, somatic signs associated with adrenergic modulation. Given the role of noradrenergic circuitry of the extended amygdala in opioid withdrawal, we examined adrenergic receptor gene expression in the bed nucleus of stria terminalis (BST) and central nucleus of the amygdala. Relative to LR, HR rats exhibit a selective increase in b 1 adrenergic receptor expression in lateral and medial BST. To uncover the functional relevance of this difference, we microinjected betaxolol, a selective b 1 receptor antagonist, into dorsal BST and assessed somatic and affective responses during withdrawal. Betaxolol microinjection dose-dependently decreased teeth chattering episodes in HR to levels observed in LR animals. Moreover, the antagonist blocked conditioned place aversion, a measure of negative affect associated with withdrawal, in HR but not in LR animals. Our results reveal for the first time that reactivity to novelty predicts somatic and affective aspects of opiate dependence, and that b 1 receptors in BST are implicated in opiate withdrawal but only in novelty-seeking individuals.

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Section: Experiments Iii: Measurement Of Place Aversionmentioning

confidence: 99%

β1 Adrenergic Receptors in the Bed Nucleus of Stria Terminalis Mediate Differential Responses to Opiate Withdrawal

Cecchi

Capriles

Watson

et al. 2006

Neuropsychopharmacol

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“…Furthermore, even though Narp knockout (KO) mice perform normally on a variety of learning tasks, they are deficient in reward devaluation learning (Johnson et al, 2007). In addition, Narp expression is enriched in several limbic system areas, including the amygdala (Reti and Baraban, 2003), PFC (Lu et al, 2002), and orexin neurons of the hypothalamus (Reti et al, 2002a) that have been implicated in mediating drug-induced behaviors (Hyman et al, 2006;Carr and Kalivas, 2006). Accordingly, to investigate the role of Narp in drug abuse, we have, in this study, assessed the performance of Narp KO mice in two behaviors induced by morphine: locomotor sensitization and conditioned place preference.…”

Section: Introductionmentioning

confidence: 99%

Narp Deletion Blocks Extinction of Morphine Place Preference Conditioning

Crombag

Dickson

Dinenna

et al. 2008

Neuropsychopharmacol

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As drug abuse can be viewed as a maladaptive form of neuronal plasticity, attention has focused on defining the synaptic plasticity mechanisms that mediate the long-term effects of these drugs. As Narp is secreted at synaptic sites and binds to the extracellular surface of AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. Accordingly, to assess its potential role in the long-lasting behavioral effects of drugs of abuse, we have investigated the impact of Narp deletion on sustained behavioral responses elicited by repeated morphine administration. Narp knockout mice display normal locomotor sensitization and conditioned place preference, but are markedly resistant to extinction of place preference. Thus, these findings indicate that Narp plays a selective role in extinction, possibly by its effects on AMPA receptor trafficking.

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“…In addition, overexpression of recombinant Narp increases the number of excitatory synapses, suggesting a role for it in excitatory synaptogenesis (Tsui et al, 1996;O'Brien et al, 1999). Moreover, Narp expression is regulated by synaptic activity and psychoactive drugs and has been suggested to play a role in molecular adaptations to drug exposure (Tsui et al, 1996;Reti and Baraban, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Although Narp is expressed throughout the CNS, its colocalization with orexin in the lateral hypothalamus (Reti et al, 2002) suggests that it may play an important role in motivational function (Lu et al, 2002;Reti and Baraban, 2003). Hypothalamic orexin neurons project to several brain regions implicated in various aspects of motivation and reward learning, including the amygdala, nucleus accumbens, ventral tegmental area, and prefrontal cortex (Peyron et al, 1998;Sakurai et al, 1998;Fadel and Deutch, 2002), and Narp itself is expressed in many of these regions as well (Tsui et al, 1996;Lu et al, 2002;Reti et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

A Selective Role for Neuronal Activity Regulated Pentraxin in the Processing of Sensory-Specific Incentive Value

Johnson¹,

Crombag²,

Takamiya³

et al. 2007

J. Neurosci.

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Neuronal activity regulated pentraxin (Narp) is a secreted neuronal product which clusters AMPA receptors and regulates excitatory synaptogenesis. Although Narp is selectively enriched in brain, its role in behavior is not known. As Narp is expressed prominently in limbic regions, we examined whether Narp deletion affects performance on tasks used to assess motivational consequences of foodrewarded learning. Narp knock-out (KO) mice were unimpaired in learning simple pavlovian discriminations, instrumental lever pressing, and in acquisition of at least two aspects of pavlovian incentive learning, conditioned reinforcement and pavlovian-instrumental transfer. In contrast, Narp deletion resulted in a substantial deficit in the ability to use specific outcome expectancies to modulate instrumental performance in a devaluation task. In this task, mice were trained to respond on two levers for two different rewards. After training, mice were prefed with one of the two rewards, devaluing it. Responding on both levers was then assessed in extinction. Whereas control mice showed a significant preference in responding on the lever associated with the nondevalued reward, Narp KO mice responded equally on both levers, failing to suppress responding on the lever associated with the devalued reward. Both groups consumed more of the nondevalued reward in a subsequent choice test, indicating Narp KO mice could distinguish between the rewards themselves. These data suggest Narp has a selective role in processing sensory-specific information necessary for appropriate devaluation performance, but not in general motivational effects of reward-predictive cues on performance.

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Opiate Withdrawal Induces Narp in the Extended Amygdala

Cited by 25 publications

References 31 publications

β1 Adrenergic Receptors in the Bed Nucleus of Stria Terminalis Mediate Differential Responses to Opiate Withdrawal

β1 Adrenergic Receptors in the Bed Nucleus of Stria Terminalis Mediate Differential Responses to Opiate Withdrawal

Narp Deletion Blocks Extinction of Morphine Place Preference Conditioning

A Selective Role for Neuronal Activity Regulated Pentraxin in the Processing of Sensory-Specific Incentive Value

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