The facilitative effects of d-cycloserine on extinction of a cocaine-induced conditioned place preference can be long lasting and resistant to reinstatement

Paolone, Giovanna; Botreau, Fanny; Stewart, Jane

doi:10.1007/s00213-008-1280-y

Cited by 91 publications

(101 citation statements)

References 21 publications

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“…The latter is unlikely because E 2 would have also interfered with reconsolidation of extinction and our design employed repeated and prolonged exposure to the context, which favors the formation of extinction memories (Mamiya et al 2009). Moreover, there is substantial evidence that E 2 treatment enhances memory consolidation in other learning paradigms (Packard and Teather 1997;Gresack and Frick 2006a), and emerging evidence that cognitive enhancers administered during the consolidation window can facilitate extinction of cocaine (Botreau et al 2006;Paolone et al 2009) or amphetamine CPP (Schroeder and Packard 2003). Although the mnemonic and neural mechanisms underlying E 2 -induced enhancement of extinction remain unknown, the present experiments are the first to demonstrate that E 2 facilitates extinction of cocaine seeking in female rats.…”

Section: Discussionmentioning

confidence: 60%

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17b-estradiol (E 2 ) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E 2 treatment followed by 2 d of vehicle treatment, or were injected with E 2 daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E 2 levels during conditioning did not affect subsequent CPP expression. During extinction, daily E 2 administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E 2 -treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E 2 could rescue extinction in these rats, half were given daily E 2 treatment and half were given vehicle. E 2 -treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E 2 is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E 2 levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.Gonadal hormones render women more susceptible than men to developing compulsive patterns of psychostimulant use. Natural fluctuations in levels of the primary ovarian hormones, estrogens and progesterone, account for this increased abuse liability. Higher levels of estrogens, and lower levels of progesterone, are associated with greater sensitivity to the euphorigenic properties of cocaine in women (Evans 2007). This increased sensitivity may contribute to why women, compared with men, start using cocaine regularly at a younger age (Chen and Kandel 2002), transition from use to abuse more quickly (McCance-Katz et al. 1999), experience greater craving in response to drug-associated cues (Robbins et al. 1999) and stress (Potenza et al. 2012;Waldrop et al. 2012), and exhibit more severe drug-seeking behavior upon relapse (Gallop et al. 2007). In contrast, more women than men remain abstinent after treatment (Weiss et al. 1997). Thus, women are both more susceptible to cocaine abuse and, paradoxically, more responsive to treatment.A substantial literature supports that estrogens mediate the enhancement of drug seeking observed in females (Febo et al. 2002;Larson et al. 2007;Segarra et al. 2010; Kerstetter and Kippin 2011), but little is known regarding the role of estrogens during treatment. Preclinically, treatment is modeled through ext...

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Section: Discussionmentioning

confidence: 60%

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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“…This persistent conditioned hyperactivity in the SRÀ/À subjects supports the conclusion that intact NMDA receptor signaling is critical to extinction learning. This genetic evidence builds upon pharmacological findings with augmented GMS activation (Paolone et al, 2009;Thanos et al, 2009;Myers and Carlezon, 2010) in models of drug-associated conditioning and suggests that NMDA receptor hypofunction may be a pathophysiological feature that increases susceptibility to addiction by inhibiting the extinction of conditioned behavior. Acquisition of behavioral sensitization was also affected by altered GMS activation, with the GlyT1À/ + subjects showing a hastened rate of acquisition and the SRÀ/À subjects showing a delayed rate.…”

Section: Discussionmentioning

confidence: 76%

“…Recent research has demonstrated that inhibiting presynaptic glutamate inhibitory autoreceptors, and thus augmenting glutamatergic synaptic neurotransmission, reduced craving in cocaine-addicted patients (Amen et al, 2011). Preclinical work with the GMS partial agonist Dcycloserine demonstrates that the selective potentiation of NMDA receptor signaling may be an effective means of enhancing extinction of drug conditioning (Paolone et al, 2009;Thanos et al, 2009;Myers and Carlezon, 2010), in a manner similar to the extinction of conditioned fear in agoraphobic patients (Ressler et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, potentiation of NMDA receptor neurotransmission, with the GMS partial agonist D-cycloserine, has been used as a strategy to facilitate the extinction of place conditioning (Paolone et al, 2009;Thanos et al, 2009;Myers and Carlezon, 2010). These findings point to the potential therapeutic benefit of enhancing NMDA receptor signaling, but questions remain as to whether aberrant NMDA receptor function may contribute to genetic susceptibility to addiction.…”

Section: Introductionmentioning

confidence: 99%

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Altered Acquisition and Extinction of Amphetamine-Paired Context Conditioning in Genetic Mouse Models of Altered NMDA Receptor Function

Benneyworth

Coyle

2012

Neuropsychopharmacol

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Repeated intermittent exposure to amphetamine (AMPH) results in the development of persistent behavioral and neurological changes. When drug exposure is paired with a specific environment, contextual cues can control conditioned responses, context-specific sensitization, and alterations in dendritic morphology in the nucleus accumbens (NAc). Intact N-methyl-D-aspartate (NMDA) glutamate receptor signaling is thought to be required for associative learning. The acquisition of context-specific behavioral sensitization to AMPH and extinction of conditioned hyperactivity have been investigated in two genetically modified mouse strains: the serine racemase homozygous knockout (SRÀ/À) and glycine transporter 1 heterozygous mutant (GlyT1À/ + ). These strains have reciprocally altered NMDA receptor co-agonists, D-serine and glycine, levels that result in decreased (SRÀ/À) or increased (GlyT1À/ + ) NMDA receptor signaling. AMPH-induced changes in dendritic morphology in the NAc were also examined. SRÀ/À mice showed reduced expression of context-specific sensitization and conditioned hyperactivity. However, the conditioned hyperactivity in these mice is completely resistant to extinction. Extinction reversed AMPH-induced increased in NAc spine density in wild-type but not SRÀ/À mice. GlyT1 À/ + mice showed a more rapid acquisition of sensitization, but no alteration in the extinction of conditioned hyperactivity. The SRÀ/À data demonstrate that a genetic model of NMDA receptor hypofunction displays a reduced ability to extinguish conditioned responses to drug-associated stimuli. Findings also demonstrate that the morphological changes in the NAc encode conditioned responses that are sensitive to extinction and reduced NMDA receptor activity. NMDA receptor hypofunction may contribute to the comorbidity of substance abuse in schizophrenia.

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“…Unfortunately, most of what is known about the neural mechanisms of extinction learning was derived from studies that use aversive conditioning (e.g., footshock) or appetitive conditioning with natural rewards (e.g., food). The extinction of conditioned fear in both animals and humans [69][70][71][72][73][74][75][76][77][78][79][80] as well as a cocaine CPP [81][82][83] can be facilitated by the cognitive enhancing drug D-4-amino-3-isoxazolidone [D-cycloserine (DCS)], which is a partial agonist at the strychnine-insensitive glycine site of Nmethyl-D-aspartate (NMDA) receptors [84,85]. Nic Dhonnchadha and colleagues recently found that DCS enhances the extinction learning process and inhibits reacquisition of drug self-administration in rats trained to self-administer cocaine [86].…”

Section: The Neurobiological Substrates Of Extinction Learningmentioning

confidence: 99%

Neuroanatomical Structures Underlying the Extinction of Drug-Seeking Behavior

Cleva¹,

Gass²

2013

TOADDJ

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This review summarizes current knowledge about the neurobiological components underlying the extinction of drug-associated memories and how they may contribute to the treatment of drug addiction. Evidence suggests that extinction learning is not the forgetting, or unlearning, of the associations between external stimuli and drug effects, but that new reinforcer expectancies are necessary for extinction of drug-seeking behavior to take place. Several theories suggest that addiction is a disorder of learning and memory, and recent evidence indicates that the brain circuits, neurotransmitters, and signal transduction mechanisms that underlie drug addiction are similar to those that mediate learning and memory processes. According to these theories, drug addiction results from repeated drug use and the formation of lasting associations between a drug's effects, withdrawal symptoms, and the environmental cues and contexts within which they are experienced. Unfortunately, standard behavioral modification techniques, such as cue exposure therapy, have shown only moderate efficacy in reducing and/or extinguishing the salience of drug-associated cues and contexts. Therefore, a greater understanding of the neurobiological mechanisms involved in the extinction of drug-related memories could provide novel therapeutic interventions for the treatment of drug addiction.

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The facilitative effects of d-cycloserine on extinction of a cocaine-induced conditioned place preference can be long lasting and resistant to reinstatement

Cited by 91 publications

References 21 publications

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

Altered Acquisition and Extinction of Amphetamine-Paired Context Conditioning in Genetic Mouse Models of Altered NMDA Receptor Function

Neuroanatomical Structures Underlying the Extinction of Drug-Seeking Behavior

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