Amphetamine models of paranoid schizophrenia: An overview and elaboration of animal experimentation.

Kokkinidis, Larry; Anisman, Hymie

doi:10.1037/0033-2909.88.3.551

Cited by 246 publications

(55 citation statements)

References 188 publications

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“…The repeated administration of amphetamine-like psychostimulants produces enduring alterations in the behavioral response to subsequent drug administration. The behavioral adaptations include the induction of paranoia in humans, which has been modeled in rodents as the induction of a sensitized motor stimulant response to psychostimulant injection (Kokkinidis and Anisman 1980;Segal and Schuckit 1983;Robinson and Becker 1986). This animal model has been extensively employed over the last decade to elucidate the cellular adaptations that underlie the behavioral changes associated with repeated psychostimulant use.…”

mentioning

confidence: 99%

Context-specific Enhancement of Glutamate Transmission by Cocaine

Bell

Duffy

Kalivas

2000

Neuropsychopharmacology

131

120

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The repeated injection of cocaine causes an increase in the capacity of a subsequent acute injection to elevate extracellular glutamate levels in the nucleus accumbens, and the present study sought to determine if the elevation in extracellular glutamate is regulated by the pairing of environmental stimuli with drug administration. Three treatment groups were injected daily for seven days with saline or cocaine (15 mg/kg, ip); 1) injection of saline in the home cage, 2) injection of cocaine in the home cage (cocaineunpaired), and 3) injection of cocaine in the test apparatus (cocaine-paired). Three weeks following the last daily injection dialysis probes were placed into the nucleus accumbens and all rats were injected with saline followed by cocaine. Basal levels of extracellular glutamate were significantly reduced in the cocaine-paired treatment group. The repeated administration of amphetamine-like psychostimulants produces enduring alterations in the behavioral response to subsequent drug administration. The behavioral adaptations include the induction of paranoia in humans, which has been modeled in rodents as the induction of a sensitized motor stimulant response to psychostimulant injection (Kokkinidis and Anisman 1980;Segal and Schuckit 1983;Robinson and Becker 1986). This animal model has been extensively employed over the last decade to elucidate the cellular adaptations that underlie the behavioral changes associated with repeated psychostimulant use. The research effort has been guided by two facts; 1) a critical molecular site of action for amphetamine-like psychostimulants is the dopamine transporter (Reith et al. 1986;Ritz et al. 1990; although see Rocha et al. 1998), and 2) dopa- NO . 3 mine transmission in the mesocorticolimbic dopamine projection from the ventral tegmental area to the nucleus accumbens is critical for the rewarding and motor stimulant actions of this class of drugs (Koob et al. 1993). Knowledge of the molecular action has precipitated the discovery of many cocaine-induced, dopamine-dependent neuroadaptations in the nucleus accumbens (see Nestler et al. 1993; White and Kalivas 1998, for reviews). Arising from this considerable research effort is the awareness that neither the emphasis on dopamine transmission nor the focus on the nucleus accumbens provides a complete profile of the neuroadaptations produced by repeated cocaine (Pierce and Kalivas 1997;Bardo 1998;Wolf 1998). Moreover, only in the cocaine-paired group did the cocaine injection elevate extracellular glutamate. Repeated administration of cocaine also produces an enduring increase in the motor stimulant response to an acute cocaine injection and it was previously found that administration of the ␣ -amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainic acid glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione inhibited the sensitized, but not the acute motor, response to cocaine. In this study it was found that the motor stimulant response elicited by cocaine was blunted by pretreatment of t...

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mentioning

confidence: 99%

Context-specific Enhancement of Glutamate Transmission by Cocaine

Bell

Duffy

Kalivas

2000

Neuropsychopharmacology

131

120

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“…It is noteworthy that in the present study we were unable to detect any relationship between injection site in either the CPU or the NA and behavior. Kokkinidis and Anisman (1980) also argue that the sites of dopamine activity responsible for locomotion and stereotypy have not been identified. They suggest that locomotion and stereotypy are likely to be mediated by the interaction of several neuroregulator systems and through a complex series of feedback loops encompassing several brain areas.…”

Section: Discussionmentioning

confidence: 99%

“…Because the behavioral response to d-amphetamine is one of the most widely used animal models of schizophrenia (Groves & Rebec, 1976;Kokkinidis & Anisman, 1980;Meltzer & Stahl, 1976), considerable effort has been devoted to understanding the neural mechanisms that mediate d-amphetamine-induced behaviors. One fundamental question is whether damphetamine's varying behavioral effects are produced by the drug's action on different brain areas.…”

Section: Microinjections Of D-amphetamine Into Thementioning

confidence: 99%

“…One fundamental question is whether damphetamine's varying behavioral effects are produced by the drug's action on different brain areas. A number of researchers have suggested that d-amphetamine-induced locomotor activity is mediated primarily by dopamine neurons in the nucleus accumbens whereas amphetamine-induced stereotypy is mediated by dopamine neurons in the caudateputamen (e.g., Jackson, Anden, & Dahlstrom, 1975;Kelly Saviour, & Iversen, 1975;Pijnenburg, Honig, & Van Rossum, 1975 pects of the same behavioral repertoire-the implication being that the different behaviors are not necessarily mediated by different dopamine systems (see Kokkinidis & Anisman, 1980, and Rebec & Bashore, 1982, for reviews).…”

Section: Microinjections Of D-amphetamine Into Thementioning

confidence: 99%

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Microinjections of d-amphetamine into the nucleus accumbens and caudate-putamen differentially affect stereotypy and locomotion in the rat

1984

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For 3 days, rats received daily bilateral microinjections of d-amphetamine or saline into either the nucleus accumbens or the caudate putamen. On Days 1 and 3, each animal was tested for stereotypy and locomotion (number of grid crossings). Microinjections of d-amphetamine into the nucleus accumbens but not the caudate putamen produced an increase in locomotion but had no effect on stereotypy, whereas d-amphetamine microinjections into the caudate-putamen but not the nucleus accumbens produced an increase in stereotypy but had no effect on locomotion, The results are discussed in terms of the role of limbic and striatal dopamine systems in mediating these behaviors.

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“…Animals first reduce exploration, then with higher doses begin repetitive actions, then with still higher doses show behavioral stereotypy (Klawans & Margolin 1975; Kokkinidis & Anisman 1983). Human amphetamine abusers show a similar progression (Kokkinidis & Anisman 1980). The initial euphoric state wanes as norepinephrine depletes and the remaining active neuromodulator is dopamine (Antelman & Caggiula 1977).…”

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confidence: 97%

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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Amphetamine models of paranoid schizophrenia: An overview and elaboration of animal experimentation.

Cited by 246 publications

References 188 publications

Context-specific Enhancement of Glutamate Transmission by Cocaine

Context-specific Enhancement of Glutamate Transmission by Cocaine

Microinjections of d-amphetamine into the nucleus accumbens and caudate-putamen differentially affect stereotypy and locomotion in the rat

Steps to a neurochemistry of personality

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