Summary
The effects of chronic caffeine administration on both adenosine and benzodiazepine receptors were studied in mouse brain membranes. Animals were fed on a diet enriched with caffeine (600 mg/kg diet) for 15 days and sacrificed 2, 4, 8 and 15 days after withdrawal. Compared with controls fed on a regular diet, animals receiving a caffeine-enriched diet showed an increase in the number of brain adenosine receptors labeled with [3H]-DPX in both the cerebellum and forebrain regions. This up-regulation was still significant 15 days after withdrawal in the cerebellum but not in the forebrain, where the number of adenosine receptors returned to control levels within 8 days following withdrawal. Benzodiazepine receptors labeled by [3H]-B-CCE were not influenced by chronic caffeine diet or withdrawal.
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References
Boulenger J-P, Patel J, Marangos PJ (1982) Effects of caffeine and theophylline on adenosine and benzodiazepine receptors in human brain. Neurosci Lett 30: 161–166
Boulenger J-P, Patel J, Post RM, Parma AM, Marangos PJ (1983) Chronic caffeine consumption increases the number of brain adenosine receptors. Life Sci 332: 1135–1142
Boulenger J-P, Marangos PJ, Zander KJ, Hanson J (1986) Stress and caffeine: effects on central adenosine receptors. Clin Neuropharmacol 9: 79–83
Braestrup C, Neilson M, Neilsen EB, Lyon M (1979) Benzodiazepine receptors in the brain are affected by different stresses: the changes are small and not unidirectional. Psychopharmacology 65: 273–277
Bruns RF, Lu GH, Pugsley TA (1987) Adenosine receptor subtypes: binding studies. In: Gerlach E, Becker BF (eds) Topics and perspectives in adenosine research. Springer, Berlin Heidelberg New York Tokyo, pp 59–73
Burt CR, Creese I, Snyder S (1977) Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196: 326–328
Carney JM (1982) Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol 75: 451–454
Chou DT, Khan S, Forde J, Hirsh KR (1985) Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence. Life Sci 36: 2347–2358
Daly JW, Butts-Lamb P, Padgett W (1983) Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cell Mol Neurobiol 3: 69–80
Daval JL, Vert P (1986) Effect of chronic exposure to methylxanthines on diazepam cerebral binding in female rats and their offspring. Dev Brain Res 27: 175–180
Finn IB, Holtzman SG (1987) Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity. Psychopharmacology 93: 428–434
Fredholm BB (1982) Adenosine actions and adenosine receptors after 1 week treatment with caffeine. Acta Physiol Scand 115: 283–292
Gilbert AM (1976) Caffeine as a drug of abuse. In: Gibbins AJ, Israel Y, Kalant H, Popham RE, Schmidt W, Smart RG (eds) Research advances in alcohol and drug problems. J Wiley, New York, pp 49–176
Greden JF (1980) Caffeine and tobacco dependence. In: Kaplan HI, Freedman AM, Sadock BT (eds) Comprehensive textbook of psychiatry, vol 2, 3rd edn. Williams & Wilkins, Baltimore, pp 1645–1652
Griffiths RR, Woodson PP (1988) Caffeine physical dependence: a review of human and laboratory animal studies. Psychopharmacology 94: 437–451
Marangos PJ, Paul SM, Goodwin FK (1979) Putative endogenous ligands for the benzodiazepine receptor. Life Sci 25: 1093–1102
Marangos PJ, Boulenger J-P, Patel J (1984) Effects of chronic caffeine on brain adenosine receptors: anatomical and ontogenetic studies. Life Sci 34: 899–907
Murray TF (1982) Up-regulation of rat cortical adenosine receptors following chronic administration and theophylline. Eur J Pharmacol 82: 113–114
Ramkumar V, Bumgarner JR, Jacobson KA, Stiles GL (1988) Multiple components of the A1 adenosine receptor-adenylate cyclase system are regulated in rat cerebral cortex by chronic caffeine ingestion. J Clin Invest 82: 242–247
Schlosberg AJ (1983) Temperature responses in rats after acute and chronic administration of caffeine. Pharmacol Biochem Behav 18: 935–942
Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW (1981) Adenosine receptors and the behavioural actions of methylxanthines. Proc Natl Acad Sci USA 78: 3260–3264
Weir RL, Hruska RE (1983) Interaction between methylxanthines and the benzodiazepine receptor. Arch Int Pharmacodyn Ther 265: 42–48
Williams M (1987) Purinergic receptors and central nervous system function. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 289–301
Wu PH, Coffin VL (1984) Up-regulation of brain [3H]diazepam binding sites in chronic caffeine-treated rats. Brain Res 294: 186–189
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Study performed when both authors were working within the Biological Psychiatry Branch. National Institute of Mental Health, Bethesda, Maryland, U.S.A.
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Boulenger, J.P., Marangos, P.J. Caffeine withdrawal affects central adenosine receptors but not benzodiazepine receptors. J. Neural Transmission 78, 9–15 (1989). https://doi.org/10.1007/BF01247109
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DOI: https://doi.org/10.1007/BF01247109