Repeated cocaine exposure inhibits the adrenocorticotropic hormone response to the serotonin releaser d-fenfluramine and the 5-HT1A agonist, 8-OH-DPAT

Levy, Andrew; Li, Q.; Kar, Louis D. Van de

doi:10.1016/0028-3908(94)90063-9

Cited by 34 publications

(12 citation statements)

References 31 publications

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“…Whereas acute administration of cocaine stimulates the hypothalamic-pituitary-adrenal axis in rats (Rivier and Vale, 1987;Levy et al, 1991), chronic cocaine administration is associated with neuroadaptive changes that lead to attenuated responses to cocaine in rats and humans (Levy et al, 1993;Zhou et al, 2003). Rats chronically treated with cocaine showed a deficit in serotonergic nerve terminal function as seen from a reduced ACTH response to serotonin-releasing drugs p-cloroamphetamine and fenfluramine (Levy et al, 1994b;Van de Kar et al, 1995). On the other hand, withdrawal from cocaine is associated with activation of the hypothalamic-pituitary-adrenal axis in rats (Peltier et al, 2001;Zhou et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα_q and Gα₁₁ Proteins in Rats Undergoing Withdrawal

Carrasco¹,

Damjanoska²,

D’Souza³

et al. 2004

J Pharmacol Exp Ther

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One of the characteristics of drug dependence is that a drug has to be administered repeatedly before withdrawal effects can be observed. We have previously shown that withdrawal after 14 days of cocaine treatment produces a supersensitivity of hypothalamic 5-hydroxytryptamine (serotonin) 2A (5-HT 2A ) receptors, which is accompanied by increases in the levels of G␣ q and G␣ 11 proteins. Unfortunately, the exact duration of cocaine treatment necessary to induce alterations in G protein levels during cocaine withdrawal is unknown. The present study investigated the minimum cocaine treatment period required to produce changes in protein levels of membrane-and cytosol-associated G␣ q and G␣ 11 proteins in the hypothalamic paraventricular nucleus, amygdala, and frontal cortex. Rats were injected with cocaine (15 mg/kg i.p., b.i.d.) for 0, 1, 3, 5, and 7 days and tested after 2 days of withdrawal. The levels of G␣ q and G␣ 11 proteins were increased in the paraventricular nucleus and the amygdala but not in the frontal cortex. Although 1 and 3 days of cocaine treatment were sufficient to maximally elevate the protein levels of G␣ 11 and G␣ q proteins in the amygdala, 5 days of treatment were required to maximally increase the levels of G␣ 11 and G␣ q proteins in the paraventricular nucleus. The data suggest that the amygdala shows a faster neuroadaptation to the effects of cocaine than the hypothalamic paraventricular nucleus. These findings provide insight into the relative importance of individual components of 5-HT 2A receptor signal transduction system in regulating the overall sensitivity of this signaling in cocaine-treated rats.

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Section: Discussionmentioning

confidence: 99%

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα_q and Gα₁₁ Proteins in Rats Undergoing Withdrawal

Carrasco¹,

Damjanoska²,

D’Souza³

et al. 2004

J Pharmacol Exp Ther

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“…Changes in the functional status of the 5-HT 2 R systems appear to follow repeated cocaine exposures as well, however, the use of widely variant doses and regimens of cocaine administration (predominantly, investigator-delivered), and 5-HT 2 R ligands which lack specificity are likely to contribute to the mixed directional changes. Serotonergic receptor function is reportedly altered in rodents during withdrawal from repeated cocaine exposure (Baumann and Rothman, 1996; Darmani, et al, 1992; Filip, et al, 2006; Levy, et al, 1994) and in abstinent human cocaine abusers (Ghitza, et al, 2007; Handelsman, et al, 1998; Lee and Meltzer, 1994; Patkar, et al, 2006). Response-independent chronic cocaine exposure regimens investigated to date did not indicate robust effects on either 5-HT 2A R or 5-HT 2C R mRNA or protein expression (Javaid, et al, 1993; Johnson, et al, 1993; Neisewander, et al, 1994), however, long-term cocaine self-administration was associated with increased 5-HT 2A R availability in the frontal cortex of monkeys (Sawyer, et al, 2012).…”

Section: Intersection Of Impulsivity and Cue Reactivity In Cocainementioning

confidence: 99%

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

2014

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Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction.

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“…In the case of L-tryptophan-induced HTR, it therefore appears that cocaine-induced postsynaptic 5-HT2A receptor supersensitivity cannot sufficiently compensate for the cumulating deficits in several components of presynaptic serotonin function. Withdrawal from such chronic cocaine exposure also persistently attenuates the capacity of d-fenfiuramine (a 5-HT releaser) to either produce the HTR (Darmani, 1997b) or to release neuroendocrine hormones (Baumann et al, 1995;Levy et al, 1994). Thus, these studies suggest that cocaine abstinence produces presynaptic deficits in several components of serotonin neurochemistry.…”

Section: Discussionmentioning

confidence: 79%

Prolonged deficits in presynaptic serotonin function following withdrawal from chronic cocaine exposure as revealed by 5-HTP-induced head-twitch response in mice

Darmani

Shaddy

Elder

1997

J. Neural Transmission

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Recent in vivo microdialysis studies have indicated that presynaptic deficits occur in brain 5-HT neurochemistry during cocaine withdrawal. The purpose of the present study was to utilize the head-twitch response (HTR) produced by 5-hydroxytryptophan (5-HTP) to investigate the dose- and time-response effects of this deficit. The HTR is considered to be a sensitive model for activation of central postsynaptic 5-HT2A receptors in rodents. Thus, different groups of mice were injected with cocaine twice daily (0, 0.1, 0.5, 2.5, 5 or 10 mg/kg, i.p.) for 7 or 13 days. During HTR testing, at 24 h following last injection, the treated mice received either 1) no cocaine; 2) their corresponding daily dose as challenge injection; or 3) a 10 mg/kg challenge dose. In a second series of experiments, extended abstinence studies were performed under the conditions of experimental protocols 1 and 2 for both 7- and 13-day cocaine (0, 0.5 and 5 mg/kg, twice daily) exposure regimens at 24, 48, 72 and 96 h following last cocaine injection. In protocol 3, the effects of a 10 mg/kg challenge dose of cocaine were studied following prolonged withdrawal from chronic cocaine exposure (0, 0.5, 5 and 10 mg/kg, twice daily for 7 and 13 days) at 24, 96 and 240 h abstinence. In experimental protocol 1 at 24 h abstinence in the 7 day exposure group, only lower doses of cocaine (0.5-2.5 mg/kg) significantly attenuated the 5-HTP-induced HTR. The deficit in 0.5 mg/kg group persisted up to 72 h abstinence. Although in the 13 day cocaine exposure groups (experimental paradigm 1) mean HTRs were generally reduced, they however failed to attain statistical significance throughout the 96 h abstinence. In protocol 2 very low challenge doses of cocaine (0.1-0.5 mg/kg) in their corresponding pretreatment groups significantly reduced the behavior at diverse abstinence intervals in both 7- and 13-day exposure regimens relative to their chronically vehicle-treated controls which had received a vehicle challenge injection during HTR testing. Unlike small doses of cocaine, larger challenge doses (5-10 mg/kg) of the stimulant potentiated the HTR score at various abstinence periods. However, the degree of the potentiations are considerably less than the ability of acute cocaine administration in enhancing the 5-HTP-induced HTR. The 10 mg/kg challenge injection in experimental protocol 3 at 24 h abstinence in the 7-day exposed mice attenuated the 5-HTP-induced HTR in 0.5, 5 and 10 mg/kg cocaine-treated groups relative to their chronic vehicle-treated controls receiving a 10 mg/kg challenge cocaine injection. The deficit in chronic 10 mg/kg cocaine-exposed mice persisted up to 240 h postcocaine abstinence. On the other hand, in the 13-day regimen, the challenge 10 mg/kg dose exhibited significant potentiations at 24 h and at 96 h for 5 and 0.5 mg/kg chronic cocaine doses respectively, but it also produced significant deficits in 0.5 and 10 mg/kg chronic doses of cocaine at 240 h abstinence. Overall, the present results suggest that enduring deficits occur in presyna...

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Repeated cocaine exposure inhibits the adrenocorticotropic hormone response to the serotonin releaser d-fenfluramine and the 5-HT1A agonist, 8-OH-DPAT

Cited by 34 publications

References 31 publications

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα_q and Gα₁₁ Proteins in Rats Undergoing Withdrawal

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα_q and Gα₁₁ Proteins in Rats Undergoing Withdrawal

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

Prolonged deficits in presynaptic serotonin function following withdrawal from chronic cocaine exposure as revealed by 5-HTP-induced head-twitch response in mice

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Repeated cocaine exposure inhibits the adrenocorticotropic hormone response to the serotonin releaser d-fenfluramine and the 5-HT1A agonist, 8-OH-DPAT

Cited by 34 publications

References 31 publications

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gαq and Gα11 Proteins in Rats Undergoing Withdrawal

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gαq and Gα11 Proteins in Rats Undergoing Withdrawal

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

Prolonged deficits in presynaptic serotonin function following withdrawal from chronic cocaine exposure as revealed by 5-HTP-induced head-twitch response in mice

Contact Info

Product

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Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα_q and Gα₁₁ Proteins in Rats Undergoing Withdrawal

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα_q and Gα₁₁ Proteins in Rats Undergoing Withdrawal