ReviewNeural substrates of cognitive inflexibility after chronic cocaine exposure
Section snippets
Cognitive flexibility in normal animals
Long-standing evidence has implicated the OFC in cognitive flexibility. Thus, OFC damage in many species causes severe reversal deficits while preserving a normal ability to learn initial contingencies (Bohn et al., 2003, Brown and McAlonan, 2003, Chudasama and Robbins, 2003, Dias et al., 1996, Izquierdo et al., 2004, Jones and Mishkin, 1972, Kim and Ragozzino, 2005, Meunier et al., 1997, Rolls et al., 1994, Schoenbaum et al., 2002, Schoenbaum et al., 2003a, Teitelbaum, 1964). In order to
Effects of cocaine exposure on information processing in orbitofrontal cortex
Many lines of evidence suggest that the structure and function of OFC is disrupted in users of addictive drugs, both in response to drug-associated cues and in the context of cognitive paradigms (Jentsch and Taylor, 1999, Schoenbaum et al., 2006, Schoenbaum and Shaham, 2008, Volkow and Fowler, 2000). Imaging studies in cocaine (Volkow et al., 1991) and methamphetamine (Volkow et al., 2001) users reveal altered metabolism in the OFC and, in cocaine users, abnormal neuronal activation in response
Effects of cocaine exposure on information processing in basolateral amygdala and striatum
As described above, the flexibility of encoding of cue significance in ABL depends on the integrity of OFC. Damage to OFC causes abnormally inflexible encoding in ABL, and the resulting miscoding of the old associations during reversals seems to be the proximal cause of the reversal impairment caused by OFC lesions. Based on this evidence, one might expect that encoding of cue significance in ABL might also be inflexible after drug exposure in addicts and models of addiction. Indeed, evidence
Conclusions
The brain regions discussed in this review, particularly OFC, ABL and ventral striatum, are all closely interconnected in a circuit that is integrally involved in learning and guiding behavior based on positive and negative outcomes. Thus it is perhaps not surprising, in light of current theories of addiction, that all three regions show marked and persistent changes after cocaine exposure. What is remarkable, however, is that each of these regions shows selective and different changes in
References (107)
- et al.
Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers
Neuropsychologia
(2001) - et al.
Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward?
Neuropsychologia
(2002) - et al.
Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum
Neuron
(2008) - et al.
Orbital prefrontal cortex and guidance of instrumental behavior in rats under reversal conditions
Behavioural Brain Research
(2003) - et al.
Neural systems and cue-induced cocaine craving
Neuropsychopharmacology
(2002) - et al.
Responses of amygdala single units to odors in the rat
Experimental Neurology
(1972) Drug addiction as dopamine-dependent associative learning disorder
European Journal of Pharmacology
(1999)- et al.
Representation of spatial goals in rat orbitofrontal cortex
Neuron
(2006) - et al.
Reactivity of limbic neurons of the monkey to appetitive and aversive signals
Electroencephalography and Clinical Neurophysiology
(1971) - et al.
Drug abusers show impaired performance in a laboratory test of decision making
Neuropsychologia
(2000)
Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys
Neuropsychopharmacology
Limbic lesions and the problem of stimulus-reinforcement associations
Experimental Neurology
Memory and addiction: shared neural circuitry and molecular mechanisms
Neuron
The involvement of the orbitofrontal cortex in learning under changing task contingencies
Neurobiology of Learning and Memory
Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior
Neuron
Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys
Neuropsychologia
Rat amygdaloid neuron responses during auditory discrimination
Neuroscience
Neural responses during anticipation of a primary taste reward
Neuron
Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat
Neuron
Primate orbitofrontal cortex and adaptive behaviour
Trends in Cognitive Sciences
The neural basis of drug craving: an incentive-sensitization theory of addiction
Brain Research: Brain Research Reviews
Structural plasticity associated with exposure to drugs of abuse
Neuropharmacology
Encoding of time-discounted rewards in orbitofrontal cortex is independent of value representation
Neuron
Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms
Neuropsychopharmacology
Investigating the neurocognitive deficits associated with chronic drug misuse
Current Opinion in Neurobiology
Rapid associative encoding in basolateral amygdala depends on connections with orbitofrontal cortex
Neuron
Orbitofrontal cortex, decision-making and drug addiction
Trends in Neurosciences
Encoding predicted outcome and acquired value in orbitofrontal cortex during cue sampling depends upon input from basolateral amygdala
Neuron
The role of orbitofrontal cortex in drug addiction: a review of preclinical studies
Biological Psychiatry
Muscarinic receptor antagonism in the basolateral amygdala blocks acquisition of cocaine-stimulus association in a model of relapse to cocaine-seeking behavior in rats
Neuroscience
Neural encoding in ventral striatum during olfactory discrimination learning
Neuron
Basolateral amygdala lesions abolish orbitofrontal-dependent reversal impairments
Neuron
A comparison of effects of orbitofrontal and hippocampal lesions upon discrimination learning and reversal in the cat
Experimental Neurology
Behavioral and neural mechanisms of compulsive drug seeking
European Journal of Pharmacology
Neural signals related to emotional learning and behavior in monkey amygdala
Society for Neuroscience Abstracts
Choosing the lesser of two evils, the better of two goods: specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice
Journal of Neuroscience
Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat
Behavioural Brain Research
Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats
Learning & Memory
Basolateral amygdala neurons encode cocaine self-administration and cocaine-associated cues
Journal of Neuroscience
Limbic activation during cue-induced cocaine craving
American Journal of Psychiatry
Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task
Cerebral Cortex
Dissociable contributions of the orbitofrontal and infralimbic cortex to Pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex
Journal of Neuroscience
Stimuli associated with a single cocaine experience elicit long-lasting cocaine-seeking
Nature Neuroscience
Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists
Proceedings of the National Academy of Sciences of the United States of America
Impulsivity and rapid discounting of delayed hypothetical rewards in cocaine-dependent individuals
Experimental and Clinical Psychopharmacology
Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task
Journal of Neurophysiology
Evidence for addiction-like behavior in the rat
Science
Dissociation in prefrontal cortex of affective and attentional shifts
Nature
The human amygdala and orbital prefrontal cortex in behavioural regulation
Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences
Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans
Psychopharmacology (Berlin)
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2021, Neurobiology of AgingCitation Excerpt :Clatworthy et al., 2009) found that young healthy subject's orally administered methylphenidate had the least cognitive flexibility in reversal learning when associated with the greatest amount of striatal dopamine release; however, spatial working memory performance was improved with increasing amounts of striatal dopamine. Similarly studies of cocaine-use found that cognitive flexibility was selectively impaired, with some studies showing that working memory remained unaffected (Colzato et al., 2009; Stalnaker et al., 2009). Combined, these experiments support the findings from this study that increased synaptic dopamine, either by reducing dopamine transporters or treatment with dopamine-enhancing drugs, can impair behavioral flexibility in healthy subjects, or patients not treated with enhancing drugs, by causing an “over-dose” of dopamine in regions with optimal dopamine levels, in relation to other dopamine depleted regions resulting in distinct functional changes, that is, no effect on working memory, but a decrease in behavioral flexibility as seen here in 6-month old treated zebrafish compared to controls.