Acute Cocaine Administration Depresses Cortical Activity

Trantham-Davidson, Heather; Lavín, Antonieta

doi:10.1038/sj.npp.1300482

Cited by 20 publications

(17 citation statements)

References 37 publications

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“…Human chronic cocaine users have been shown to have deficits in measures of attention [see 34, for a review], while dysfunction in prefrontal cortex activity has been implicated for attentional deficits in several studies of drug abusers [6,7,24,25,30,32,47]. Thus, it is possible that cocaine directly disrupted the circuits required for learning and memory in fear conditioning.…”

Section: Discussionmentioning

confidence: 99%

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Wood

Fay

Sage

et al. 2007

Behavioural Brain Research

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Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1 -15 mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15 mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1 mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine's anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine's reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning. KeywordsHippocampus; Amygdala; Freezing; Memory A growing body of evidence supports the view that drugs of abuse interfere with many aspects of cognitive functioning. For example, cocaine use has been linked to deficits in such cognitive areas as attention, cognitive flexibility, and short-term and working memory [34,43]. However, these findings in humans are controversial as cocaine use is naturally confounded with many other variables [e.g. 23, 27, 31]. Some studies, in fact, provide evidence for enhancement of certain cognitive abilities in cocaine users [e.g. 27, 50]. Relatively few studies in animals have examined the effects of cocaine on learning outside of the realm of addiction (e.g. selfadministration, place preference, sensitization). Indeed, several studies have focused on the mechanisms underlying addiction, including structural plasticity [see 41 for review], but few have examined the acute, behavioral effects of cocaine in rodents on simple learning and memory paradigms. We believe that most researchers implicitly assume, as we once did, that cocaine, as a psychostimulant, would naturally enhance learning and memory. However, evidence now exists linking cocaine use with specific cognitive deficits [5,25,34,43] as well as with general problems such as unemployment [35]. Moreover, a view has emerged that addictive drugs such as cocaine may work by taking control of critical reinforcement-related learning and memory circuits in the brain [28]. If cocaine modulates such circuits, then it may 1 Address correspondence and reprint requests to: Suzanne C. Wood,

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Section: Discussionmentioning

confidence: 99%

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Wood

Fay

Sage

et al. 2007

Behavioural Brain Research

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“…In anesthetized rats, acute cocaine causes depolarization, eliminates the oscillation between down and up states, and decreases the firing rate of these neurons (Trantham-Davidson and Lavin, 2004). It is possible that elimination of membrane oscillation prevents PFC neurons from reaching the up state and thus is responsible for the decrease in firing rate.…”

Section: Discussionmentioning

confidence: 99%

Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

2006

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One of the core symptoms of cocaine addiction is compulsive drug-seeking behavior. Although the precise neural substrates are unknown, it has been hypothesized that this behavior involves cocaine-induced hypofunction of the prefrontal cortex (PFC) or "hypofrontality." To test this hypothesis, PFC neuronal activity was monitored in rats during ϳ3 weeks of cocaine self-administration (SA). Rats were trained to press a lever to self-administer cocaine in daily 2 h sessions. Responding was reinforced contingent on a modified fixed-ratio 5 schedule of reinforcement. In the first SA session, the overall firing rate and burst rate were significantly decreased after cocaine infusions relative to the period immediately before the session. These effects disappeared after Ն10 d of drug SA and were replaced by a significant increase in burst duration and firing rate within a burst. Notably, however, the level of basal activity before the first drug infusion of each SA session decreased significantly after multiple weeks of cocaine exposure. Collectively, these data support the view that although repeated sessions of cocaine SA decrease basal PFC activity, increased burst-related firing in response to cocaine infusions suggests that processing of cocaine-related information is enhanced and may contribute to increased control by cocaine over cocaine-seeking behavior.

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“…For example, cocaine elicits an increase in cerebrovascular resistance and a decrease in carotid blood flow (Stankovic et al, 1998) and an increase in blood pressure. In addition, repeated cocaine administration has been shown to increase voltage-sensitive calcium currents in response to membrane depolarization in prefrontal cortex pyramidal neurons (Uchimura and North, 1990;White and Kalivas, 1998;Trantham-Davidson and Lavin, 2004;Nasif et al, 2005). These data combined with the well known role of intracellular calcium as a "final common pathway to cell death" (Schanne et al, 1979) led us to hypothesize that the toxic effects of cocaine in the brain may in part be related to changes in [Ca 2ϩ ] i .…”

Section: Introductionmentioning

confidence: 97%

Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects

Du¹,

Yu²,

Volkow³

et al. 2006

J. Neurosci.

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Cocaine abuse increases the risk of life-threatening neurological complications such as strokes and seizures. Although the vasoconstricting properties of cocaine underlie its cerebrovascular effects, the mechanisms underlying its neurotoxicity remain incompletely understood. ] i in the brain. The effects of cocaine were compared with those of methylphenidate, which has similar catecholaminergic effects as cocaine (except for serotonin increases) but no local anesthetic properties, and of lidocaine, which has similar local anesthetic effects as cocaine but is devoid of catecholaminergic actions. To control for the hemodynamic effects of cocaine, we assessed the effects of cocaine in animals in which normal blood pressure was maintained by infusion of phenylephrine, and we also measured the effects of transient hypotension (mimicking that induced by cocaine). We show that cocaine induced significant increases (ϳ10 -15%) in [Ca 2ϩ ] i that were independent of its hemodynamic effects and of the anesthetic used (isofluorance or ␣-chloralose).

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Acute Cocaine Administration Depresses Cortical Activity

Cited by 20 publications

References 37 publications

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects

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