Caffeine elevates reinforcement threshold for electrical brain stimulation: tolerance and withdrawal changes

Caffeine dose-dependently increased the reinforcement threshold for electrical self-stimulation of the brain in rats, which is opposite to the effect of other behavioral stimulants. Tolerance to this effect of caffeine developed rapidly with daily drug administration. Abrupt cessation of daily drug treatment was followed by decreases in reinforcement threshold and response rate lasting 24-48 h, changes consistent with a drug withdrawal phenomenon. Because caffeine has the characteristics of a drug of abuse, these results question the generality of hypotheses relating the abuse potential of a drug to its ability to sensitize brain reward systems.

[1]  H. Fibiger.  Drugs and reinforcement mechanisms: a critical review of the catecholamine theory. , 1978, Annual review of pharmacology and toxicology.

[2]  K. E. Moore,et al.  Amphetamines: Biochemical and Behavioral Actions in Animals , 1978 .

[3]  P. B. Dews,et al.  Behavioral effects of caffeine , 2020, Caffeine and Behavior: Current Views & Research Trends.

[4]  W. Woolverton,et al.  Behavioral dependence produced by continuous phencyclidine infusion in rhesus monkeys. , 1984, The Journal of pharmacology and experimental therapeutics.

[5]  G. Spiller.  The Methylxanthine beverages and foods : chemistry, consumption, and health effects , 1984 .

[6]  M. Fernstrom,et al.  Effects of Caffeine on Monoamine Neurotransmitters in the Central and Peripheral Nervous System , 1984 .

[7]  C. Gallistel,et al.  Affinity for the dopamine D2 receptor predicts neuroleptic potency in blocking the reinforcing effect of MFB stimulation , 1983, Pharmacology Biochemistry and Behavior.

[8]  R. Griffiths,et al.  Human coffee drinking: reinforcing and physical dependence producing effects of caffeine. , 1986, The Journal of pharmacology and experimental therapeutics.

[9]  L. Stein.  SELF-STIMULATION OF THE BRAIN AND THE CENTRAL STIMULANT ACTION OF AMPHETAMINE. , 1964, Federation proceedings.

[10]  D T Chou,et al.  Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence. , 1985, Life sciences.

[11]  J. Liebman.  Discriminating between reward and performance: A critical review of intracranial self-stimulation methodology , 1983, Neuroscience & Biobehavioral Reviews.

[12]  R. Michael,et al.  Ethanol and current thresholds for brain self-stimulation in the lateral hypothalamus of the rat. , 1987, Alcohol.

[13]  J. Carney,et al.  EFFECTS OF CAFFEINE, THEOPHYLLINE AND THEOBROMINE ON SCHEDULED CONTROLLED RESPONDING IN RATS , 1982, British journal of pharmacology.

[14]  S G Holtzman,et al.  Tolerance to caffeine-induced stimulation of locomotor activity in rats. , 1986, The Journal of pharmacology and experimental therapeutics.

[15]  S. Holtzman,et al.  Operant behavior in the morphine-dependent rhesus monkey. , 1973, The Journal of pharmacology and experimental therapeutics.

[16]  S H Snyder,et al.  Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. , 1981, Life sciences.

[17]  L. Harris,et al.  Dependence on tetrahydrocannabinol in rhesus monkeys. , 1986, The Journal of pharmacology and experimental therapeutics.

[18]  R. Michael,et al.  Task-specific effects of nicotine in rats Intracranial self-stimulation and locomotor activity , 1986, Neuropharmacology.

[19]  R. Wise,et al.  Neuroleptic-induced attenuation of brain stimulation reward in rats. , 1978, Journal of comparative and physiological psychology.

[20]  C. Kornetsky,et al.  Cocaine: Acute effects of reinforcement thresholds for self-stimulation behavior to the medial forebrain bundle , 1978, Pharmacology Biochemistry and Behavior.

[21]  Boulenger Jp,et al.  Caffeine consumption and anxiety: preliminary results of a survey comparing patients with anxiety disorders and normal controls. , 1982 .

[22]  S H Snyder,et al.  Adenosine receptors and behavioral actions of methylxanthines. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[23]  S. Holtzman,et al.  Development and maintenance of morphine tolerance and dependence in the rat by scheduled access to morphine drinking solutions. , 1978, The Journal of pharmacology and experimental therapeutics.

[24]  S G Holtzman,et al.  Complete, reversible, drug-specific tolerance to stimulation of locomotor activity by caffeine. , 1983, Life sciences.

[25]  C. Kornetsky,et al.  Intracranial self-stimulation thresholds: a model for the hedonic effects of drugs of abuse. , 1979, Archives of general psychiatry.

[26]  R. Wise.  Action of drugs of abuse on brain reward systems , 1980, Pharmacology Biochemistry and Behavior.

[27]  R. Post,et al.  Caffeine: relationship to human anxiety, plasma MHPG and cortisol. , 1984, Psychopharmacology bulletin.

[28]  S. Iversen,et al.  Handbook of Psychopharmacology , 1988, Springer US.

[29]  L. Pellegrino,et al.  stereotaxic atlas of the rat brain , 1967 .

[30]  S. Holtzman,et al.  Free-operant and auto-titration brain self-stimulation procedures in the rat: A comparison of drug effects , 1979, Pharmacology Biochemistry and Behavior.

[31]  B A Berkowitz,et al.  Release of norepinephrine in the central nervous system by theophylline and caffeine. , 1970, European journal of pharmacology.