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Background: Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement.
Aims: This rat study was conducted to determine if nicotine self-administration is altered by co-administration of the complex mixture of compounds in tobacco smoke extract (TSE).
Methods: Female Sprague-Dawley rats were tested for self-administration of low doses of nicotine (3 or 10 µg/kg/infusion) at three different rates of reinforcement (FR1, FR3 and FR5) over three weeks either alone or together with the complex mixture of tobacco smoke extract (TSE).
Results: Rats self-administering 3 µg/kg/infusion of nicotine alone showed a rapid initiation on an FR1 schedule, but declined with FR5. Rats self-administering nicotine in TSE acquired self-administration more slowly, but increased responding over the course of the study. With 10 µg/kg/infusion rats self-administered significantly more nicotine alone than rats self-administering the same nicotine dose in TSE. Rats self-administering nicotine alone took significantly more infusions with the 10 than the 3 µg/kg/infusion dose, whereas rats self-administering nicotine in TSE did not. Nicotine in TSE led to a significantly greater locomotor hyperactivity at a dose of 0.1 mg/kg compared to rats that received nicotine alone. Rats self-administering nicotine alone had significantly more responding on the active vs. inactive lever, but rats self-administering the same nicotine doses in TSE did not.
Conclusions: Self-administration of nicotine in a purer form appears to be more clearly discriminated and dose-related than nicotine self-administered in the complex mixture of TSE.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.109073 | DOI Listing |
ACS Appl Mater Interfaces
August 2025
College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Hypertension is a major risk factor for cardiovascular diseases and needs effective blood pressure reduction. Current antihypertensive drugs, such as captopril, face challenges, including the enzymatic degradation and the liver first-pass effect. Here, we developed a dissolving microneedle (MN) loaded with a peptide-based enzyme-responsive prodrug peptide-captopril (PC) to enhance the stability of captopril and enable efficient transdermal delivery.
View Article and Find Full Text PDFNat Commun
July 2025
Zhejiang Provincial Key Laboratory of Addiction Research, The affiliated Kangning Hospital of, Ningbo University, Ningbo, P.R. China.
Methamphetamine (METH) addiction involves escalating intake with strong cue reactivity, and high relapse risk, yet its neural mechanism remains unclear. Using c-Fos mapping and machine learning, we identified the claustrum (CLA), a subcortical region reciprocally connected with the anterior cingulate cortex (ACC), as key mediators of both METH taking and seeking in self-administering male rats. Chemogenetic inhibition of CLA suppressed both drug consumption and cue-induced reinstatement, while ACC inhibition selectively reduced drug-seeking.
View Article and Find Full Text PDFPsychopharmacology (Berl)
July 2025
Department of Pharmacology, Toxicology & Neuroscience, School of Medicine, Louisiana State University Health Shreveport, Shreveport, LA, 71104, USA.
Background: Methamphetamine is a psychostimulant with significant public health implications. Chronic methamphetamine use is linked to profound dysregulation of the dopaminergic system, cognitive deficits, and psychiatric symptoms. While traditional experimenter administered "binge" dosing models reliably produce dopaminergic neurotoxicity, they fail to capture the volitional, drug intake characteristic of human methamphetamine use.
View Article and Find Full Text PDFPharmacol Biochem Behav
September 2025
Department of Pharmacology & Physiology, College of Medicine, Drexel University, Philadelphia, PA, USA. Electronic address:
Cocaine use disorder remains a persistent public health dilemma that currently lacks effective treatment strategies. One key impediment to successful treatment outcomes is increased drug craving that occurs over the course of abstinence and subsequent relapse to drug use. This phenomenon, known as the incubation of drug craving, has been modeled extensively in rodent models of intravenous drug self-administration.
View Article and Find Full Text PDFPharmacol Biochem Behav
July 2025
NMPA Key Laboratory of Quality Monitoring of Anaesthetic and Psychotropic Substances, Chongqing Institute for Food and Drug Control, No.1 Chunlan Second Road, Yubei District, Chongqing 401121, China. Electronic address:
Crisugabalin, a novel third-generation ligand targeting the α2δ subunit of voltage-gated calcium channels, has been approved in China for the treatment of pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Existing research suggests that ligands for the α2δ subunit of voltage-gated calcium channels may carry a risk of abuse. To evaluate the abuse potential of crisugabalin, five well-recognized animal models were utilized in these preclinical studies.
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