Caffeine tolerance: Behavioral, electrophysiological and neurochemical evidence
Autor: | Chou Dorothy T, Jesse Forde, Hirsh Kenneth R, Sukur Khan |
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Rok vydání: | 1985 |
Předmět: |
Male
Action Potentials Receptors Cell Surface Motor Activity Pharmacology Reticular formation General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Neurochemical Mesencephalon Drug tolerance Caffeine medicine Animals General Pharmacology Toxicology and Pharmaceutics Neurons Reticular Formation Receptors Purinergic Drug Tolerance General Medicine Adenosine Adenosine receptor Rats chemistry Analeptic Reticular connective tissue medicine.drug |
Zdroj: | Life Sciences. 36:2347-2358 |
ISSN: | 0024-3205 |
DOI: | 10.1016/0024-3205(85)90325-x |
Popis: | The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of [3H]-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify the neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, our data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for [3H]-CHA was observed in reticular formation membranes without any change in receptor affinity. We propose, therefore, that up-regulation of adenosine receptors may underlie the development of tolerance to the CNS effects of caffeine. |
Databáze: | OpenAIRE |
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