Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy

Barr, Gordon A.; Sharpless, Nansie S.; Cooper, Stanley D.; Schiff, Stanley; Paredes, William; Bridger, Wagner H.

doi:10.1016/0024-3205(83)90817-2

Cited by 123 publications

(56 citation statements)

References 15 publications

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“…Consistent with the well-established conditioned reactivity to cocaine cues in humans, classically conditioned behavioral responses to cocaine can be readily elicited in animals (10)(11)(12)(13)(14). However, it has been more difficult to demonstrate motivating effects of stimuli conditioned to cocaine in animal models of relapse.…”

mentioning

confidence: 77%

Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens

Weiss

Maldonado-Vlaar

Parsons

et al. 2000

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

381

327

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The conditioning of the pharmacological actions of cocaine with environmental stimuli is thought to be a critical factor in the longterm addictive potential of this drug. Cocaine-related stimuli may increase the likelihood of relapse by evoking drug craving, and brain-imaging studies have identified the amygdala and nucleus accumbens (NAcc) as putative neuroanatomical substrates for these effects of cocaine cues. To study the significance of environmental stimuli in the recovery of extinguished cocaine-seeking behavior, male Wistar rats were trained to associate discriminative stimuli (S⌬s) with response-contingent availability of intravenous cocaine vs. saline. The rats then were subjected to repeated extinction sessions during which cocaine, saline, and the respective S⌬s were withheld until the animals reached an extinction criterion of <4 responses over three consecutive sessions. Subsequent re-exposure to the cocaine S⌬, but not the nonreward S⌬, produced strong recovery of responding at the previously active lever in the absence of any further drug availability. The efficacy and behavioral selectivity of the cocaine S⌬ remained unaltered throughout an 8-day test period. Exposure to the cocaine S⌬ significantly increased dopamine efflux in the NAcc and amygdala as measured by intracranial microdialysis in a separate group of rats. Dopamine levels remained unaltered in the presence of the nonreward S⌬. The results demonstrate that cocaine-predictive stimuli elicit robust and persistent cocaine-seeking behavior, and that this effect may involve activation of dopamine transmission in the NAcc and amygdala.T he classical conditioning of the pharmacological actions of cocaine with environmental stimuli is thought to have an important role in the long-term addictive potential of this drug. Environmental cues repeatedly associated with the subjective effects of cocaine can elicit drug craving (1-6) and possibly, automatic behavioral responses (7,8) that may lead to relapse in recovering cocaine addicts. Whereas the role of drug-related stimuli in motivating the resumption of drug use is not fully understood, such learned responses may be among the most important factors responsible for the high rates of relapse associated with cocaine and other drug addiction (9).Consistent with the well-established conditioned reactivity to cocaine cues in humans, classically conditioned behavioral responses to cocaine can be readily elicited in animals (10-14). However, it has been more difficult to demonstrate motivating effects of stimuli conditioned to cocaine in animal models of relapse. Stimuli paired contiguously with cocaine infusions in self-administering rats can reinstate responding following extinction (15-17), but these stimuli often produce only weak and transient effects (16,17), or fail to elicit cocaine-seeking behavior (18,19). The lack of robust and enduring behavioral effects of cocaine cues in many ''reinstatement'' studies appears inconsistent with the presumed strength and persistence of the motivating effe...

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mentioning

confidence: 77%

Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens

Weiss

Maldonado-Vlaar

Parsons

et al. 2000

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

381

327

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“…These Pavlovian conditioned responses may contribute to the maintenance of drug-taking habits in active cocaine users, and promote relapse in detoxified addicts. In rats, environments associated with cocaine evoke conditioned locomotor activation in the absence of the drug (Barr et al 1983;Cervo and Samanin 1996;DiCiano et al 1998a;Stewart et al 1984). This Pavlovian conditioned behavioral activation may be analogous to some of the conditioned subjective and physiological responses elicited by cocaine-related stimuli in human drug addicts (Pert 1994).…”

mentioning

confidence: 99%

Involvement of the Nucleus Accumbens and Medial Prefrontal Cortex in the Expression of Conditioned Hyperactivity to a Cocaine-Associated Environment in Rats

Franklin

Druhan

2000

Neuropsychopharmacology

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This study examined the roles of the nucleus accumbens (NAc), medial prefrontal cortex, basolateral amygdala, and ventral subiculum of the hippocampus in the expression of Pavlovian conditioned hyperactivity responses to cocainerelated stimuli. This was accomplished by pharmacologically inhibiting these regions prior to drug-free tests for conditioned hyperactivity in an environment previously associated with cocaine. The results indicate that conditioned hyperactivity could be disrupted by infusions of the baclofen (0.2 nmol/0.5 l/side) Environmental stimuli associated with cocaine use can elicit a variety of conditioned physiological and subjective responses in abstinent cocaine addicts (Childress et al. 1999;Newlin 1992). These Pavlovian conditioned responses may contribute to the maintenance of drug-taking habits in active cocaine users, and promote relapse in detoxified addicts. In rats, environments associated with cocaine evoke conditioned locomotor activation in the absence of the drug (Barr et al. 1983;Cervo and Samanin 1996;DiCiano et al. 1998a;Stewart et al. 1984). This Pavlovian conditioned behavioral activation may be analogous to some of the conditioned subjective and physiological responses elicited by cocaine-related stimuli in human drug addicts (Pert 1994). Accordingly, studies of the neurobiological mechanisms underlying conditioned behavioral activation in rats may provide valuable information that could facilitate the development of pharmacological treatments for cocaine addiction.Several lines of evidence suggest that the nucleus accumbens (NAc) may regulate the expression of conditioned responses to stimuli associated with cocaine or other psychostimulants. For example, 6-OHDA lesions of mesoaccumbens dopamine terminals post-conditioning can interfere with conditioned hyperactivity elicited NO . 6 by an environment repeatedly paired with amphetamine (Gold et al. 1988). Moreover, exposure to cocaine-or amphetamine-related cues increases dopamine release within the NAc (DiCiano et al. 1998a,b;Fontana et al. 1993;Gratton and Wise 1994), alters NAc cell firing (Bowman et al. 1996;Giampoala et al. 1999), and induces conditioned increases in Fos-related protein within the caudal NAc (Franklin and Druhan 2000;Neisewander et al. 2000; although see Brown and Fibiger 1992). Together, these studies suggest that the NAc may be important for the expression of conditioned hyperactivity responses to psychostimulantpaired stimuli.Cortical and limbic regions that project to the NAc also may regulate conditioned responses to psychostimulant-related cues. Indeed, lesions or pharmacological manipulations of the medial prefrontal cortex (mPFC), the basolateral amygdala (Bl), and the ventral subiculum of the hippocampus (vSub) disrupt the stimulus control of operant drug-seeking responses measured in place-preference, conditioned reinforcement, or self-administration procedures (Brown and Fibiger 1993; Hiroi and White 1991; Phillips 1997, 1998;Isaac et al. 1989;Tzschentke and Schmidt 1998;Whitelaw et al...

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“…There is experimental evidence of a conditioned increase in extracellular dopamine after contextcocaine association [40], and higher concentrations of the dopamine metabolite homovanillic acid in mesolimbic and caudate regions after contextamphetamine and context-apomorphine pairings as compared to pseudoconditioned control groups [51]. However, there are also conflicting results indicating no change in dopamine metabolite concentrations using cocaine as the CS [52]. Hopefully, understanding how the neuropsychological mechanisms are activated by both drug action and environmental associations will provide new strategies to approach the treatment of psychiatric syndromes characterized by malfunctioning of the dopaminergic system.…”

Section: Discussionmentioning

confidence: 99%

Prepulse inhibition modulation by contextual conditioning of dopaminergic activity

Mena¹,

Casa²

2013

Behavioural Brain Research

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Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy

Cited by 123 publications

References 15 publications

Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens

Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens

Involvement of the Nucleus Accumbens and Medial Prefrontal Cortex in the Expression of Conditioned Hyperactivity to a Cocaine-Associated Environment in Rats

Prepulse inhibition modulation by contextual conditioning of dopaminergic activity

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