Time-Dependent Effects of Repeated Amphetamine Treatment on Norepinephrine in the Hypothalamus and Hippocampus Assessed with In Vivo Microdialysis

We studied the influence of cocaine use on the structure of neurons in brain regions that contribute to its rewarding effects by allowing rats to self-administer cocaine (0.33 mg/infusion) for 1 h a day for 1 month. Control animals were left undisturbed or allowed to work for food for the same period of time. After an additional 1 month drug-free period the brains were processed for Golgi-Cox staining. In rats that self-administered cocaine, but not rats that worked for food, there was a significant increase in dendritic branching and in the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens and on pyramidal cells in the prefrontal and parietal (but not occipital) cortex. There was also a 2.6-fold increase in the incidence of spines with multiple heads (branched spines) on medium spiny neurons. Finally, in the prefrontal cortex some of the apical dendrites of pyramidal cells appeared misshaped, having large bulbous structures on their terminal tips. We speculate that cocaine self-administration experience alters patterns of synaptic connectivity within limbocortical circuitry that is thought to contribute to cocaine's incentive motivational effects and may have neuropathological effects in frontal areas involved in decision making and judgment. Together, these two classes of drug-induced neuroadaptations may contribute to the development of addiction. Synapse 39:257-266, 2001.

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Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex

Robinson

Gorny

Mitton

et al. 2001

Synapse

359

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The Long-Term Behavioral and Neurobiological Consequences of Treatment with Psychomotor Stimulant Drugs: Implications for Psychopathology

Robinson¹

2000

Contemporary Issues in Modeling Psychopathology

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Long-lasting sensitization of reward-directed behavior by amphetamine

Mendez

Williams

Bhavsar

et al. 2009

Behavioural Brain Research

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Exposure to psychostimulant drugs of abuse such as amphetamine can result in long-lasting "sensitization" of reward-directed behavior, such that subjects display enhancements in behavior directed by and toward rewards and reward-predictive cues (i.e. -"incentive sensitization"). The purpose of these experiments was to determine the degree to which such sensitization resulting from chronic amphetamine exposure influences both appetitive and consummatory food-motivated behavior. Adult male Long-Evans rats received daily i.p. injections of d-amphetamine (2.0 mg/kg) or saline vehicle for five consecutive days. This amphetamine exposure regimen produced lasting sensitization to the acute locomotor stimulant effect of the drug. One month after drug exposure rats were tested for instrumental responding (lever pressing) for food reward under various response schedules. Two months after drug exposure, rats were tested for food consumption in a discriminative Pavlovian context-potentiated eating task, involving pairings of one context with food and another context with no food. Amphetamine-exposed rats showed significantly greater instrumental responding for food reward than saline controls, particularly under conditions of high response ratios. In the potentiated eating task, testing under conditions of food satiation revealed that amphetamineexposed rats ate significantly more than saline controls in the food-paired context. These experiments demonstrate that amphetamine exposure can cause enduring increases in both appetitive and consummatory aspects of natural reward-directed behavior. Such long-lasting incentive sensitization could account in part for the propensity for relapse in drug addiction, as well as for reported enhancements in non-drug reward-related behavior.

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Time-Dependent Effects of Repeated Amphetamine Treatment on Norepinephrine in the Hypothalamus and Hippocampus Assessed with In Vivo Microdialysis

Cited by 13 publications

References 60 publications

Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex

Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex

The Long-Term Behavioral and Neurobiological Consequences of Treatment with Psychomotor Stimulant Drugs: Implications for Psychopathology

Long-lasting sensitization of reward-directed behavior by amphetamine

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