Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) has risen drastically over the past 20 years in the United States and abroad. Amphetamine-based prescription stimulants are the most prescribed treatment for ADHD and the diversion of these drugs has also increased. Reports indicate 61% of individuals with an ADHD medication prescription have sold or shared their medication. Exposure to prescription stimulants, especially for those without an ADHD diagnosis, may increase susceptibility to drugs of abuse. The present study aimed to model ADHD medication misuse during adolescence in male and female rats. The primary dependent measure was the acquisition of intravenous cocaine self-administration. Male and female, Long-Evans rats were exposed to d-amphetamine (0.7 mg/kg, i.p.) or saline in adolescence (35-41 days old), during which locomotor activity was measured. At approximately 75 days old, animals were implanted with jugular catheters. All animals then entered a 15-day acquisition procedure with no prior operant training. Finally, following acquisition all animals responded on a progressive-ratio (PR) schedule to obtain 0, 0.1, 0.3, and 1.0 mg/kg/infusion cocaine. Animals exposed to amphetamine acquired cocaine self-administration faster than saline-exposed controls when the acquisition criterion was operationally defined as two consecutive days with 12 infusions or greater. Discrete-time hazard modeling also found amphetamine exposure to increase the likelihood of acquiring cocaine self-administration. There were no differences detected during PR testing. These data suggest that individuals with histories of prescription stimulant misuse may be at increased risk to use other drugs of abuse. (PsycINFO Database Record
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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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