Tolerance and sensitization to the locomotor-activating effects of cocaine are mediated via independent mechanisms

Izenwasser, Sari; French, Dawn

doi:10.1016/s0091-3057(02)00942-5

Cited by 32 publications

(20 citation statements)

References 22 publications

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“…Moreover the lesser degree of sensitization observed after NZF-2b/7ZFMyt1 knock-down indicates a ceiling effect as the initial cocaine-induced locomotion was already strong enough that further increase was probably not possible. Tolerance and sensitization to the locomotor-activating effects of cocaine can exist simultaneously, since they are mediated by separate mechanisms (Izenwasser and French, 2002). Our results show that NZF-2b/ 7ZFMyt1 might be playing an important role in governing the animal′s responsiveness in these disparate mechanisms.…”

Section: Discussionmentioning

confidence: 77%

The brain-specific Neural Zinc Finger transcription factor 2b (NZF-2b/7ZFMyt1) causes suppression of cocaine-induced locomotor activity

Chandrasekar

Dreyer

2010

Neurobiology of Disease

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Chronic cocaine induces high expression of the brain-specific Neural-Zinc-Finger transcription factor-2b (NZF-2b/7ZFMyt1), particularly in the mesolimbic dopaminergic pathway, resulting in a 11-fold increase in NZF-2b/7ZFMyt1 expression in the Nucleus Accumbens (NAc). Overexpression of this gene in the NAc with a NZF-2b/7ZFMyt1-expressing lentivirus resulted in N55% decrease in locomotor activity upon chronic cocaine administration, compared to control animals. In contrast knocking-down the gene in the NAc with lentiviruses expressing shRNAs against NZF-2b/7ZFMyt1 induced strong hyperlocomotor activity upon cocaine. Strong inhibition of BDNF is observed upon NZF-2b/7ZFMyt1 expression, concomitant with strong induction of transcription factors REST1 (RE silencing transcription factor-1) and NAC1, probably leading to regulation of gene expression by interaction with histone deacetylases. These changes lead to decreased responsiveness of the animal to the locomotor-activating effects of cocaine, indicating that NZF-2b/7ZFMyt1 expression plays an important role in phenotypic changes induced by the drug.

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Section: Discussionmentioning

confidence: 77%

The brain-specific Neural Zinc Finger transcription factor 2b (NZF-2b/7ZFMyt1) causes suppression of cocaine-induced locomotor activity

Chandrasekar

Dreyer

2010

Neurobiology of Disease

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“…This is in comparison to a 10 mg/kg dose that enhanced locomotor activity for the first 120 min. Tolerance is typically observed when high continuous doses of cocaine are used (e.g., 40 mg/kg /day; [25]) and is customarily represented as a rightward shift in the dose-dependent relationship or a downward shift compared to saline controls. In the current experiment, the dampening of the drug effect on locomotor activity across time for the 20 mg/kg dose compared to the 10 mg/kg dose may represent the emergence of a behavior that competes with locomotor activity such as stereotypy.…”

Section: Discussionmentioning

confidence: 99%

Cocaine sensitization in male quail: Temporal, conditioning, and dose-dependent characteristics

Geary

Akins

2007

Physiology & Behavior

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Chronic cocaine administration typically results in increased locomotor activity, known as behavioral sensitization. Investigating the time course of locomotor activity across trials may provide a more detailed analysis of the temporal changes that might occur within sensitization. Prior research with rodents shows that the peak of locomotor activity shifts from acute to chronic drug administration. The purpose of the current experiment was to investigate acute versus chronic cocaine effects on locomotor activity in an avian species, Japanese quail, and to investigate whether this phenomenon is dose dependent. Subjects received daily ip injections of saline or 5, 10, or 20 mg/kg cocaine for 20 days. Following each injection, birds were placed in standard locomotor activity chambers, and activity was recorded for 150 min. A cocaine challenge was given after a ten-day withdrawal period. Two retraining trials were given to reestablish cocaine responding prior to a saline challenge in the drug-paired environment. Results showed that repeated administration of the 10 mg/kg dose of cocaine enhanced activity across 120 min compared with acute administration. In contrast, repeated administration of the 20 mg/kg dose resulted in greater cocaine-induced activity for 60 min compared with acute administration. In addition, behavioral sensitization was shown to be dose-dependent and appeared to be due, at least in part, to conditioning.

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Section: Discussionmentioning

confidence: 99%

“…There are many studies which report that repeated administration of cocaine produces behavioral sensitization (Beyer and Steketee, 1999;Bhargava and Kumar, 1997;Bohn et al, 2003;Henry and White, 1995;Izenwasser and French, 2002;Martin-Iverson and Burger, 1995;Polston et al, 2006;Post and Rose, 1976). On the other hand continuous infusion of cocaine produces tolerance (Izenwasser and French, 2002;King et al, 1999;Kunko et al, 1998). Although continuous infusion of cocaine has been shown to produce tolerance, behavioral sensitization can develop following intermittent cocaine administration even in absence of a withdrawal period (Ansah et al, 1996;Bhargava and Kumar, 1997;Polston et al, 2006;Post and Rose, 1976).…”

Section: Discussionmentioning

confidence: 99%

Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers

et al. 2007

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Recent studies suggest that calcium influx via L-type calcium channels is necessary for psychostimulant-induced behavioral sensitization. In addition, chronic amphetamine upregulates subtype Cav1.2-containing L-type calcium channels. In the present studies, we assessed the effect of calcium channel blockers (CCBs) on cocaine-induced behavioral sensitization and determined whether the functional activity of L-type calcium channels is altered after repeated cocaine administration. Rats were administered daily intraperitoneal injections of either flunarizine (40 mg/kg), diltiazem (40 mg/kg) or cocaine (20 mg/kg) and the combination of the CCBs and cocaine for 30 days. Motor activities were monitored on Day 1, and every 6th day during the 30-day treatment period. Daily cocaine administration produced increased locomotor activity. Maximal augmentation of behavioral response to repeated cocaine administration was observed on Day 18. Flunarizine pretreatment abolished the augmented behavioral response to repeated cocaine administration while diltiazem was less effective. Measurement of tissue monoamine levels on Day 18 revealed cocaine-induced increases in DA and 5-HT in the nucleus accumbens. By contrast to behavioral response, diltiazem was more effective in attenuating increases in monoamine levels than flunarizine. Cocaine administration for 18 days produced increases in calcium uptake in synaptosomes prepared from the nucleus accumbens and frontal cortex. Increases in calcium uptake were abolished by flunarizine and diltiazem pretreatment. Taken together, the augmented cocaine-induced behavioral response on Day 18 may be due to increased calcium uptake in the nucleus accumbens leading to increased dopamine (DA) and serotonin (5-HT) release. Flunarizine and diltiazem attenuated the behavioral response by decreasing calcium uptake and decreasing neurochemical release.

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Tolerance and sensitization to the locomotor-activating effects of cocaine are mediated via independent mechanisms

Cited by 32 publications

References 22 publications

The brain-specific Neural Zinc Finger transcription factor 2b (NZF-2b/7ZFMyt1) causes suppression of cocaine-induced locomotor activity

The brain-specific Neural Zinc Finger transcription factor 2b (NZF-2b/7ZFMyt1) causes suppression of cocaine-induced locomotor activity

Cocaine sensitization in male quail: Temporal, conditioning, and dose-dependent characteristics

Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers

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