The goal of the present study was to investigate the effects of intravenous cocaine administration on cerebellar Purkinje cell firing. Extracellular neuron activity was recorded and cells were locally excited with spaced microiontophoretic pulses of glutamate. Glutamate-evoked and spontaneous discharges were compared before and immediately following cocaine administration. Cocaine injections (1. 0 and 0.25 mg/kg, i.v.) induced a reversible suppression of both spontaneous activity and glutamate-evoked excitation. Procaine was ineffective in producing similar actions. Cocaine only inhibited glutamate-induced excitation in animals pre-treated with reserpine (5 mg/kg, i.p.). Propranolol injections (10 mg/kg, i.p.) were ineffective in blocking cocaine-induced inhibitions. Yohimbine (5 mg/kg, i.p.) pre-treatment abolished cocaine-induced suppressions of either spontaneous or glutamate-evoked excitation. Therefore, cocaine administration decreases Purkinje cell spontaneous and glutamate-evoked discharges by a mechanism involving alpha(2)-adrenoceptor activation. It is suggested that by changing the normal function of the cerebellum cocaine can produce drug-related alterations in overt behavior and cognition.
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http://dx.doi.org/10.1016/s0014-2999(00)00711-1 | 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 PDFbioRxiv
December 2024
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Methylglyoxal (MG) is an endogenously produced non-enzymatic side product of glycolysis that acts as a partial agonist at GABA receptors. MG that is metabolized by the enzyme glyoxalase-1 (GLO1). Inhibition of GLO1 increases methylglyoxal levels, and has been shown to modulate various behaviors, including decreasing seeking of cocaine-paired cues and ethanol consumption.
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.
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