Previous studies showed that an extended 6-h session duration produced an increasing rate of cocaine self-administration in rats. The present study further investigated the effect of dose and session duration on cocaine self-administration. Eight groups of rats (4 doses x 2 session durations) self-administered one of four cocaine doses (0.25, 0.5, 1, and 2 mg/kg/injection) in either 1- or 6-h sessions under a fixed-ratio schedule. In another experiment, two other groups of rats self-administered 0.5 mg/kg/injection of cocaine in either 3- or 12-h sessions. Cocaine self-administration increased at all doses in 6-h sessions but not in 1-h sessions. Cocaine intake (milligram/kilogram) reached an asymptote earlier at a higher dose, but the rate of responding increased faster when the dose was lower. In ShA rats, the cocaine dose-response function was higher in rats at the two higher unit doses than at the lower doses. Cocaine self-administration increased in 6- and 12-h sessions, but not in 1- and 3-h sessions. The increase in self-administration was faster and greater in 12-h sessions than 6-h sessions. The data suggest that cocaine self-administration increases at various doses with prolonged access and that an increase in the rate of responding is positively and inversely associated with session duration and unit dose, respectively. Results also imply that cocaine intake reaches a ceiling faster at high doses even under short session duration. Therefore, high doses or prolonged access to cocaine are more likely to result in a pattern of cocaine intake that reflects compulsive use.
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http://dx.doi.org/10.1124/jpet.106.113340 | DOI Listing |
Pharmacol Rep
January 2025
Department of Translational Neuroscience, Center for Addiction Research, Wake Forest University School of Medicine, 115 South Chestnut St, Winston-Salem, NC, 27101, USA.
Background: Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M mAChR subtype via positive allosteric modulation has been shown to inhibit the behavioral and neurochemical effects of cocaine across several rodent models of CUD.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Neuropharmacology Laboratory, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
Chronic cocaine use triggers inflammatory and oxidative processes in the central nervous system, resulting in impaired microglia. Mesenchymal stem cells, known for their immunomodulatory properties, have shown promise in reducing inflammation and enhancing neuronal survival. The study employed the cocaine self-administration model, focusing on ionized calcium-binding adaptor protein 1 (Iba-1) and cell morphology as markers for microglial impairment and PLX-PAD cells as a treatment for attenuating cocaine craving.
View Article and Find Full Text PDFNeuroscience
January 2025
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; Wu Tsai Institute, Yale University, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA. Electronic address:
Cocaine abstinence and withdrawal are linked to relapse, heightened anxiety, and depressive-like symptoms. While L-type calcium channels (LTCCs) have been associated with cocaine use disorders in humans and drug-seeking behavior in rodent models, their role in mood-related symptoms during cocaine abstinence remains unclear. This study examined whether blocking LTCCs with isradipine could alter anxiety and depressive symptoms induced by cocaine abstinence.
View Article and Find Full Text PDFFront Neurosci
December 2024
Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Introduction: Circadian rhythm disturbances have long been associated with the development of psychiatric disorders, including mood and substance use disorders. Adolescence is a particularly vulnerable time for the onset of psychiatric disorders and for circadian rhythm and sleep disruptions. Preclinical studies have found that circadian rhythm disruption (CRD) impacts the brain and behavior, but this research is largely focused on adult disruptions.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular and Medical Pharmacology, Geffen School of Medicine, UCLA, Los Angeles, CA 90095.
To identify genes involved in regulating the behavioral and brain transcriptomic response to the potentially addictive drug cocaine, we performed genome-wide association studies (GWASs) for intravenous self-administration of cocaine or saline (as a control) over 10 days using a panel of inbred and recombinant inbred mice. A linear mixed model increased statistical power for these longitudinal data and identified 145 loci for responding when saline only was delivered, compared to 17 for the corresponding cocaine GWAS. Only one locus overlapped.
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