Conditioned increases in mesolimbic dopamine overflow by stimuli associated with cocaine

Fontana, David; Post, Robert M.; Pert, Agu

doi:10.1016/0006-8993(93)90477-5

Cited by 127 publications

(80 citation statements)

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“…In addition, cocaine administered at the onset of the reinstatement phase increased extracellular DA, thereby increasing the sensitivity to detect phasic extracellular DA levels in all groups (Grace 1995). Consistent with this idea, conditioned DA release in the NAc is detected after a cocaine, but not a saline, challenge in a cocainepaired environment Fontana et al 1993). …”

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confidence: 77%

“…This anticipatory response may be DA mediated in some (Carelli and Deadwyler 1996), but not all cells (Chang et al 1994). Furthermore, Fontana et al (1993) found a context-dependent sensitization of both locomotor behavior and extracellular DA levels in the NAc after a cocaine challenge in a cocaine-paired environment, whereas found conditioned locomotion, but no conditioned increase in extracellular DA levels after a saline challenge. Finally, exposure to a cocaine-paired environment failed to alter Fos levels in the NAc .…”

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confidence: 96%

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Time-Dependent Changes in Cocaine-Seeking Behavior and Extracellular Dopamine Levels in the Amygdala during Cocaine Withdrawal

Tran-Nguyen

1998

Neuropsychopharmacology

257

182

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Cocaine and cocaine-associated cues elicit craving in addicts and reinstate cocaine-seeking behavior in rats. Craving and cocaine-seeking behavior may be mediated by withdrawalinduced changes in dopamine (DA) Cocaine-seeking behavior; Cocaine withdrawal; Dopamine; Amygdala; Reinstatement; Extinction; Self-administration Craving is thought to play a critical role in drug relapse (Dackis and Gold 1985;Gawin and Kleber 1986;Wallace 1989). Gawin and Kleber (1986) have suggested that early during withdrawal from a cocaine binge there is little or no craving, and that later during withdrawal there is intense craving that can be exacerbated by cocaine-paired cues. In the laboratory, addicts exposed to drug-related cues (Childress et al. 1988;Ehrman et al. 1992;Satel et al. 1995) or given a cocaine priming injection report intense craving (Jaffe et al. 1989;Kosten et al. 1992;Preston et al. 1993) and exhibit conditioned physiological changes (Ehrman et al. 1992). Similarly, animals with a history of cocaine self-administration exhibit reinstatement of extinguished cocaine-seeking behavior after presentation of cocaine-paired cues or a cocaine priming injection (Davis and Smith 1976;Stewart 1984;Stewart et al. 1984). In these studies, cocaine-seeking behavior is measured as nonreinforced lever-pressing behavior.Reinstatement of cocaine-seeking behavior may be mediated by enhanced dopamine (DA) neurotransmission because systemic administration of indirect (Gerber and Stretch 1975;de Wit and Stewart 1981;Worley et al. 1994) or direct DA receptor agonists (de Wit and Stewart 1981;Wise et al. 1990;Self et al. 1996) reinstates cocaine-seeking behavior. It has been suggested based on localization studies that the nucleus accumbens (NAc) is involved because drugs that enhance DA neu- Received September 11, 1997; revised November 7, 1997; accepted November 13, 1997. N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 19 , NO . 1 Cocaine-Seeking Behavior and Dopamine 49 rotransmission in this region reinstate cocaine-seeking behavior (Stewart 1984). Studies have also examined conditioned DA neurotransmission in the NAc after presentation of cocaine-paired cues, but the results have been controversial. After presentation of a light paired previously with cocaine self-administration, in vivo voltammetry studies have demonstrated that putative DA-related signals increase in the NAc (Gratton and Wise 1994;Kiyatkin and Stein 1994;Kiyatkin 1995), whereas an in vivo microdialysis study indicated no changes in extracellular DA levels (Neisewander et al. 1996). Electrophysiological studies have demonstrated a change in neuronal firing in the NAc prior to cocainereinforced lever pressing (Chang et al. 1994; Deadwyler 1994, 1996; Peoples and West 1996). This anticipatory response may be DA mediated in some (Carelli and Deadwyler 1996), but not all cells (Chang et al. 1994). Furthermore, Fontana et al. (1993) found a context-dependent sensitization of both locomotor behavior and extracellular DA levels in the NAc after a cocaine challenge ...

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confidence: 77%

mentioning

confidence: 96%

Time-Dependent Changes in Cocaine-Seeking Behavior and Extracellular Dopamine Levels in the Amygdala during Cocaine Withdrawal

Tran-Nguyen

1998

Neuropsychopharmacology

257

182

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“…For example, 6-OHDA lesions of mesoaccumbens dopamine terminals post-conditioning can interfere with conditioned hyperactivity elicited 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.…”

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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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“…It is interesting to consider the impact conditioned stimuli may have at this point. It has, for example, been known for some time that the expression of behavioral sensitization can come under strong conditioned stimulus control (Stewart & Vezina 1988) and this appears to be the case for sensitized NAS DA responding as well (e.g., Fontana et al 1993). If it is assumed that this stimulus control is achieved via occasion-setting or facilitation by a conditioned stimulus complex (Anagnostaras & Robinson 1996), it follows that sensitization will be evoked by an eliciting stimulus appearing in the situation surrounding or following the individual's experience of this stimulus complex.…”

Section: Conditioned Stimuli and The Expression Of Extraversion: Helpmentioning

confidence: 99%

Steps to a neurochemistry of personality

Lawrence¹,

Koepp²,

Gunn³

et al. 1999

Behav Brain Sci

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Extraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation.Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system.Individual differences in the functioning of this network arise from functional variation in the ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, "experience-expectant," and "experience-dependent." Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive context and incentive motivation and behavior.Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.Keywords: behavioral sensitization; dopamine; extraversion; heterosynaptic plasticity; incentive motivation; neurobiology; personality the behavioral, emotional, and motivational characteristics of extraversion. Next, we identified a mammalian behavior pattern with corresponding characteristics, as described in the psychological and ethological literatures. Once an analogous motivation was identified, animal neurobiological research provided empirical links to its neural organization and neurochemical modulation. These hypotheses were then extended to humans and subjected to empirical tests. Extraversion: Central characteristics and underlying motivationExtraversion is a higher-order trait that is derived from a set of correlated lower-order traits. The lower-order traits are measures of behavioral and emotional characteristicssuch as social dominance, positive emo...

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Conditioned increases in mesolimbic dopamine overflow by stimuli associated with cocaine

Cited by 127 publications

References 48 publications

Time-Dependent Changes in Cocaine-Seeking Behavior and Extracellular Dopamine Levels in the Amygdala during Cocaine Withdrawal

Time-Dependent Changes in Cocaine-Seeking Behavior and Extracellular Dopamine Levels in the Amygdala during Cocaine Withdrawal

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

Steps to a neurochemistry of personality

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