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Rationale: Previous research in humans suggests a relationship between drug abuse and impulsivity as shown by selection of a smaller immediate reward over a larger delayed reward. However, it is not clear whether impulsivity precedes drug abuse or drug abuse influences impulsivity.
Objective: The hypothesis of the present experiment was that rats selected for choosing smaller, immediate over larger, delayed food would acquire IV cocaine self-administration faster than those choosing larger, delayed food rewards.
Methods: Female rats were screened for locomotor activity and trained on a delay discounting procedure that allowed them access to two response levers and a food pellet dispenser. Under a fixed-ratio (FR) 1 schedule, responding on one lever resulted in immediate delivery of one 45 mg pellet, while responding on the other lever resulted in delivery of three 45 mg pellets after a variable delay that increased after responses on the delay lever and decreased after responses on the immediate lever. For each rat, a mean adjusted delay (MAD) was calculated for each daily session, and stability was defined as MADs varying less than 5 s across 5 days. Based on their average MADs, rats were separated into low impulsive (LoI) and high impulsive (HiI) groups, implanted with an indwelling IV catheter, and trained to lever press for cocaine (0.2 mg/kg) under an FR1 schedule.
Results: There were no differences in locomotor activity between the LoI and HiI groups; however, a greater percentage of the HiI group acquired cocaine self-administration, and they did so at a significantly faster rate than the LoI rats.
Conclusions: Performance on the delay discounting model of impulsivity predicted vulnerability to subsequent acquisition of cocaine self-administration.
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http://dx.doi.org/10.1007/s00213-004-1994-4 | DOI Listing |
bioRxiv
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.
View Article and Find Full Text PDFNeuropsychopharmacology
December 2024
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
The accumulation of GluA2-lacking Ca-permeable AMPARs (CP-AMPARs) in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) is required for the expression of incubation of cocaine craving. The exchange protein directly activated by cAMP (Epac) is an intracellular effector of cAMP and a guanine nucleotide exchange factor for the small GTPase Rap1. Epac2 has been implicated in the trafficking of AMPA receptors at central synapses.
View Article and Find Full Text PDFPharmacol Biochem Behav
December 2024
Department of Psychological Science, Creighton University, 2500 California Plaza HLSB 302, Omaha, NE 68178, United States. Electronic address:
Pharmacol Biochem Behav
November 2024
Division on Substance Use Disorders, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Irving Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Individuals seeking treatment for their cocaine use often report depressive systems and nearly half meet criteria for major depressive disorder (MDD). This descriptive study aimed to assess the effects of the antidepressant venlafaxine alone and in combination with gabapentin on depressive symptoms, subjective effects of cocaine, and cocaine self-administration in depressed and non-depressed people who use cocaine. The effects of medication condition on mood and on the effects of smoked cocaine were compared between a group of clinically depressed people who use cocaine (n = 5) and a control group of non-depressed people who use cocaine (n = 5) using laboratory-based measures.
View Article and Find Full Text PDFCell Rep
December 2024
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address:
The prelimbic cortex is involved in operant reward seeking. However, the precise nature of its activity patterns and whether/how they differ between different types of rewards are largely unknown. We use miniscope calcium imaging to observe prelimbic activity during both food and cocaine seeking in freely behaving mice.
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