Neuroadaptations of Cdk5 in Cholinergic Interneurons of the Nucleus Accumbens and Prefrontal Cortex of Inbred Alcohol‐preferring Rats Following Voluntary Alcohol Drinking

Camp, Marguerite; Mayfield, R. Dayne; McCracken, Mandy L.; McCracken, Lindsay M.; Alcantara, Adriana A.

doi:10.1111/j.1530-0277.2006.00160.x

Cited by 20 publications

(18 citation statements)

References 122 publications

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“…In the brain, Cdk5 has been implicated in diverse biochemical processes involved in both functional and structural synaptic plasticity (21,52,53). Striatal Cdk5 levels are increased in response to chronic exposure to cocaine (15) and may be altered in response to voluntary alcohol drinking (54). Although the present study focuses on the role of Cdk5 in NAc, cocaine also induces increased expression of the kinase in dorsal striatum (15), which may also inf luence cocaine's behavioral effects.…”

Section: Discussionmentioning

confidence: 85%

Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine

Taylor

Lynch

Sanchez

et al. 2007

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

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Neuronal adaptations in striatal dopamine signaling have been implicated in enhanced responses to addictive drugs. Cyclindependent kinase 5 (Cdk5) regulates striatal dopamine signaling and is a downstream target gene of the transcription factor ⌬FosB, which accumulates in striatal neurons after chronic cocaine exposure. Here we investigated the role of Cdk5 activity in the nucleus accumbens (NAc) on cocaine-induced locomotor sensitization, responding for reward-associated stimuli (conditioned reinforcement), and cocaine self-administration under a progressive ratio schedule. Repeated infusions of the Cdk5 inhibitor roscovitine into the NAc before cocaine injections augmented both the development and expression of cocaine sensitization without having any intrinsic stimulant actions of its own. Additionally, repeated intraNAc infusions of roscovitine to saline-injected rats enhanced locomotor responses to a subsequent cocaine challenge. Similar effects were found after infusions of another Cdk5 inhibitor, olomoucine, but not its inactive congener, iso-olomoucine. Repeated inhibition of Cdk5 within the NAc also robustly enhanced the incentivemotivational effects of cocaine, similar to the effect of prior repeated cocaine exposure. The enhanced responding with conditioned reinforcement induced by cocaine persisted at least 2 weeks after the final roscovitine infusion. NAc infusions of olomoucine also produced acute and enduring increases in ''breakpoints'' achieved on a progressive ratio schedule for cocaine reinforcement. These results demonstrate profound and persistent effects of NAc Cdk5 inhibition on locomotor sensitization and incentivemotivational processes and provide direct evidence for a role for striatal Cdk5-induced alterations in the brain's long-term adaptations to cocaine. addiction ͉ dopamine ͉ conditioned reinforcement

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Section: Discussionmentioning

confidence: 85%

Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine

Taylor

Lynch

Sanchez

et al. 2007

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

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“…In similar work, it has been shown that chronic ethanol drinking by P rats significantly up-regulated (~50%) cyclin-dependent kinase 5 (Cdk5, a marker of neuronal plasticity) immunoreactive cholinergic interneurons in the NAcc while significantly down-regulating (~50%) Cdk5 immunoreactive cholinergic interneurons in the infralimbic and prelimbic regions of the prefrontal cortex (Camp et al, 2006). Dopamine controls acetylcholine release and D1- and D2-like dopamine receptors have been identified on cholinergic interneurons of the NAcc (Alcantara et al., 2003, Berlanga et al, 2005).…”

Section: Discussionmentioning

confidence: 92%

Alcohol‐Preferring P Rats Emit Spontaneous 22‐28 kHz Ultrasonic Vocalizations that are Altered by Acute and Chronic Alcohol Experience

Reno

Thakore

Gonzales

et al. 2015

Alcoholism Clin & Exp Res

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Background Emotional states are often thought to drive excessive alcohol intake and influence the development of alcohol use disorders (AUDs). To gain insight into affective properties associated with excessive alcohol intake, we utilized ultrasonic vocalization (USV) detection and analyses to characterize the emotional phenotype of selectively bred alcohol-preferring “P rats”; an established animal model of excessive alcohol intake. USVs emitted by rodents have been convincingly associated with positive (50–55 kHz) and negative (22–28 kHz) affective states. Therefore, we hypothesized that 50–55 and 22–28 kHz USV emission patterns in alcohol-preferring P rats would reveal a unique emotional phenotype sensitive to alcohol experience. Methods 50–55 kHz frequency-modulated (FM) and 22–28 kHz USVs elicited from male alcohol-preferring P rats were assessed during access to water, 15% and 30% EtOH (v/v). (EtOH; n=12) or water only (Control; n=4) across 8 weeks of daily drinking-in-the-dark (DID) sessions. Results Spontaneous 22–28 kHz USVs are emitted by alcohol-naïve P rats and are enhanced by alcohol experience. During DID sessions when alcohol was not available (e.g., “EtOH OFF” intervals), significantly more 22–28 kHz than 50–55 kHz USVs were elicited, while significantly more 50–55 kHz than 22–28 kHz USVs were emitted when alcohol was available (e.g., “EtOH ON” intervals). In addition, USV acoustic property analyses revealed chronic effects of alcohol experience on 22–28 kHz USV mean frequency, indicative of lasting alcohol-mediated alterations to neural substrates underlying emotional response. Conclusions Our findings demonstrate that acute and chronic effects of alcohol exposure are reflected in changes in 22–28 and 50–55 kHz USV counts and acoustic patterns. These data support the notion that initiation and maintenance of alcohol intake in P rats may be due to a unique, alcohol-responsive emotional phenotype and further suggest that spontaneous 22–28 kHz USVs serve as behavioral markers for excessive drinking vulnerability.

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“…This reduction consists of lower numbers of Cdk5-immunoreactive cholinergic neurons in the PLC of those rats (Camp, et al, 2006). The lower numbers of PLC Cdk5-immunoreactive cholinergic neurons are concomitant with an increase in Cdk5-immunoreactive cells in the nucleus accumbens and amygdala.…”

Section: Discussionmentioning

confidence: 99%

Infusion of gliotoxins or a gap junction blocker in the prelimbic cortex increases alcohol preference in Wistar rats

2008

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Postmortem research has revealed that there is a lower density of glial cells in regions of the prefrontal cortex (PFC) of uncomplicated alcoholics when compared with control subjects. Impairment of astrocyte function in the PFC may contribute to malfunction in circuits involved in emotion-and reward-related subcortical centers, heavily connected with the PFC and directly involved in the pathophysiology of addictive behaviours. The hypothesis was tested that infusion of gliotoxins known to injure astrocytes or of a gap junction blocker into the prelimbic area of the rat PFC results in increased preference for ethanol in rats exposed to free choice between water and 10% ethanol. Fluorocitric acid, L-α-aminoadipic acid (AAD) or the gap junction blocker 18-α-glycyrrhetinic acid (AGA) were bilaterally infused once into the rat prelimbic cortex and alcohol preference (ratio of 10% ethanol consumed to total liquid ingested) was measured before and after infusion. Infusion of AAD or AGA dissolved in their vehicles, but not of their vehicles alone, resulted in significant transient increase of preference for 10% ethanol. The present data suggest that impaired integrity of glial cells or the gap junctional communication between them in the rat PFC may contribute to changes in ethanol preference.

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Neuroadaptations of Cdk5 in Cholinergic Interneurons of the Nucleus Accumbens and Prefrontal Cortex of Inbred Alcohol‐preferring Rats Following Voluntary Alcohol Drinking

Cited by 20 publications

References 122 publications

Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine

Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine

Alcohol‐Preferring P Rats Emit Spontaneous 22‐28 kHz Ultrasonic Vocalizations that are Altered by Acute and Chronic Alcohol Experience

Infusion of gliotoxins or a gap junction blocker in the prelimbic cortex increases alcohol preference in Wistar rats

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