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Behavioral Tolerance (Contingent Tolerance) isMediated in Part by Variations in Regional Cerebral Blood Flow

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Brain and Mind

Abstract

Concepts and experimental results taken frombehavioral pharmacology, functional brain imaging,brain physiology, and behavioral neuroscience, wereused to develop the hypothesis that behavioraltolerance can, in part, be attributed to cellulartolerance. It is argued that task specific activationof circumscribed neuronal populations gives rise tocorresponding increases in regional cerebral bloodflow such that neurons related to task performance areexposed to higher effective doses of blood-borne drugthan neuronal groups not highly activated by thebehavioral task. Through this cerebral hemodynamicregulatory mechanism cellular tolerance phenomena canat least partially account for behavioral tolerance(i.e., tolerance conferred through drugged practice).

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References

  • Black, J. E., Isaacs, K. R., Anderson, B. J., Alcantara, A. A. and Greenough, W. T., 1990: Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats, Proc. Natl. Acad. Sci. USA 87, 5568–5572.

    PubMed  Google Scholar 

  • Bowen, S. E., Fowler, S. C. and Kallman, M. J. (in press), Behavioral tolerance to the force differentiation effects of diazepam and midazolam, Psychopharmacology.

  • Buonomano, D. V. and Merzenich, M. M., 1998: Cortical plasticity: from synapses to maps,Ann. Rev. Neurosci. 21, 149–186.

    PubMed  Google Scholar 

  • Chen, C., 1968: A study of the alcohol tolerance effect and an introduction of a new behavioral technique, Psychopharmacologia 12, 433–440.

    PubMed  Google Scholar 

  • Chen, X., Michaelis, M. L. and Michaelis, E. K., 1997: Effects of chronic ethanol treatment on the expression of calcium transport carriers and NMDA/glutamate receptor proteins in brain synaptic membranes, J. Neurochem. 69, 1559–1569.

    PubMed  Google Scholar 

  • Cohen, Z., Bonvento, G., Lacombe, P. and Hamel, E., 1996: Serotonin in the regulation of brain microcirculation, Prog. Neurobiol. 50, 335–362.

    PubMed  Google Scholar 

  • Dolin, S. J., Patch, T. L., Rabbani, M., Taberner, P. V. and Little, H. J., 1991: Differential interactions between benzodiazepines and the dihydropyridines, nitrendipine and Bay K 8644, Neuropharmacology 30, 217–224.

    PubMed  Google Scholar 

  • Donoghue, J. P., 1985: Contrasting properties of neurons in two parts of the primary motor cortex of the awake rat, Brain Res. 333, 171–177.

    Google Scholar 

  • Donoghue, J. P. and Wise, S. P., 1982: The motor cortex of the rat: Cytoarchitecture and microstimulation mapping, J. Comp. Neur. 212, 76–88.

    PubMed  Google Scholar 

  • Fowler, S. C., 1987: Force and duration of operant response as dependent variables in behavioral pharmacology, in T. Thompson, P. B. Dews and J. E. Barrett (eds), Neurobehavioral Pharmacology, Advances in Behavioral Pharmacology, Vol. 6, Erlbaum, Hillsdale, New Jersey, pp. 83–127.

    Google Scholar 

  • Fowler, S. C., Bowen, S. E. and Kallman, M. J., 1993: Practice augmented tolerance to triazolam: Evidence from an analysis of response durations and interresponse times, Behavioural Pharmacology 4, 147–157.

    PubMed  Google Scholar 

  • Goudie, A. J. and Emmett-Oglesby, M. W. (eds), 1989: Psychoactive Drugs: Tolerance and Sensitization, Humana, Clifton, NJ.

    Google Scholar 

  • Hassler, W. and Steinmetz, H., 1987: Cerebral hemodynamics in angioma patients: an intraoperative study, J. Neurosurgery 67, 822–831.

    Google Scholar 

  • Isaacs, K. R., Anderson, B. J., Alcantara, A. A., Black, J. E. and Greenough, W. T., 1992: Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning, J. Cerebral Blood Flow Metabol. 12, 110–119.

    Google Scholar 

  • Ivry, R., 1997: Cerebellar timing systems, Int. Rev. Neurobiol. 41, 555–5573.

    PubMed  Google Scholar 

  • Kalant, H., 1989: Drug tolerance and sensitization: A pharmacological overview, in A. J. Goudie and M. W. Emmett-Oglesby (eds), Psychoactive Drugs: Tolerance and Sensitization, Humana, Clifton, NJ, pp. 547–577.

    Google Scholar 

  • Kim, J. J., Krupa, D. J. and Thompson, R. F., 1998: Inhibitory cerebello-olivary projections and blocking effect in classical conditioning, Science 279, 570–573.

    PubMed  Google Scholar 

  • Kleim, J. A., Barbay, S. and Nudo, R. J., 1998: Functional reorganization of the rat motor cortex following motor skill learning, J. Neurophysiol 80, 3321–3325.

    PubMed  Google Scholar 

  • Kosslyn, S. M., Pascual-Leone, A., Felician, O., Camposano, S., Keenan, J. P., Thompson, W. L., Ganis, G., Sukel, K. E. and Alpert, N.M., 1999: The role of area 17 in visual imagery: convergent evidence from PET and rTMS, Science 284, 167–170.

    PubMed  Google Scholar 

  • Krimer, L. S., Muly, E. C., Williams, G. V. and Goldman-Rakic, P. S. (1998) Dopaminergic regulation of cerebral cortical microcirculation, Nature Neuroscience 1, 286–289.

    PubMed  Google Scholar 

  • Littleton, J. M. and Little, H. J., 1989: Adaptation in neuronal calcium channels as a common basis for physical dependence on central depressant drugs, in A. J. Goudie and M.W. Emmett-Oglesby (eds), Psychoactive Drugs: Tolerance and Sensitization Humana, Clifton, NJ, pp. 461–518.

    Google Scholar 

  • Lynch, M. A. and Littleton, J. M., 1983: Possible association of alcohol tolerance with increased synaptic Ca2+ sensitivity, Nature 303, 175–176.

    PubMed  Google Scholar 

  • Mandeville, J. B., Marota, J. J., Kosofsky, B. F., Weissleder, R., Rosen, B. R. and Weisskoff, R. M., 1998: Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation, Magn. Reson. Med. 39, 615–624.

    PubMed  Google Scholar 

  • Mattay, V. S., Berman, K. F., Ostrem, J. L., Esposito, G., Van Horn, J. D., Bigelow, L. B. and Weinberger, D. R., 1996: Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study, J. Neurosci. 16, 4816–4822.

    PubMed  Google Scholar 

  • Messing, R. O., Carpenter, C. L., Diamond, L. and Greenberg, D. A., 1986: Ethanol regulates calcium channels in clonal neural cells, Proc. Natl. Acad. Sci. USA 83, 6213–6215.

    PubMed  Google Scholar 

  • Michaelis, E. K., Michaelis, M. L. and Kumar, K. N., 1993: Molecular properties of an NMDA receptor complex and effects of ethanol on the expression of this complex, in C. Alling et al. (eds), Alcohol, Cell Membranes and Signal Transduction in Brain, Plenum, New York, pp. 139–149.

    Google Scholar 

  • Pearson, P. P., Li, C. X., Daniels, Y. E., Fowler, S. C. and Waters, R.S., 1998: Effects of use-dependent training on the physiological organization of forepaw barrel subfield (FBS) in somatosensory cortex (SI) of adult rat, Soc. Neurosci. Abstr. 24, 635.

    Google Scholar 

  • Petersen, S. E., van Mier, H., Fiez, J. A. and Raichle, M. E., 1998: The effects of practice on the functional anatomy of task performance, Proc. Natl. Acad. Sci. USA 95, 853–860.

    PubMed  Google Scholar 

  • Poulos, C. X. and Cappell, H., 1991: Homeostatic theory of drug tolerance: a general model of physiological adaptation, Psychol. Rev. 98, 390–408.

    PubMed  Google Scholar 

  • Price, A. W. and Fowler, S. C., 1981: Deficits in contralateral and ipsilateral forepaw motor control following unilateral motor cortical ablations in rats, Brain Res. 205, 81–90.

    PubMed  Google Scholar 

  • Raichle, M. E., 1987: Circulatory and metabolic correlates of brain function in normal humans, in V. B. Mountcastle, F. Plum and S. R. Geiger (eds), Handbook of Physiology: The Nervous System, Vol. 5, Higher Functions of the Brain, Part 2, American Physiological Society, Bethesda, MD, pp. 643–674.

    Google Scholar 

  • Raichle, M. E., 1998: Behind the scenes of functional brain imaging: a historical and physiological perspective, Proc. Natl. Acad. Sci. USA 95, 765–772.

    PubMed  Google Scholar 

  • Roland, E., Gulyas, B., Seitz, R. J., Bohm, C. and Stone-Elander, S., 1990: Functional anatomy of storage, recall, and recognition of a visual pattern in man, Neuroreport 1, 53–56.

    PubMed  Google Scholar 

  • Sdao-Jarvie, K. and Vogel-Sprott, M., 1986: Mental rehearsal of a task before or after ethanol: Tolerance facilitating effects, Alcohol Drug Dependence 18, 23–30.

    Google Scholar 

  • Smith, J. B., 1991a: Situational specificity of tolerance to effects of phencyclidine on responding of rats under fixed-ratio and spaced-responding schedules, Psychopharmacology 103, 121–128.

    PubMed  Google Scholar 

  • Smith, J. B., 1991b: Situational specificity of tolerance to decreased operant responding by morphine and l-nantradol, Psychopharmacology 103, 115–120.

    PubMed  Google Scholar 

  • Sonnenschien, R. R., 1962: Circulation to the brain and spinal cord: Physiology, in D. I. Abramson (ed.), Blood Vessels and Lymphatics, Academic Press, New York, pp. 241–245.

    Google Scholar 

  • Thompson, R. F. and Krupa, D. J., 1994: Organization of memory traces in the mammalian brain, Ann. Rev. Neurosci. 17, 519–549.

    Article  PubMed  Google Scholar 

  • Vogel-Sprott, M., Rawana, E. and Webster, R., 1984: Mental rehearsal of a task under ethanol facilitates tolerance, Pharmacol. Biochem. Behav. 21, 329–331.

    PubMed  Google Scholar 

  • Whittington, M. A., Dolin, S. J., Patch, T. L., Siarey, R. J., Butterworth, A. R. and Little, H. J., 1991: Chronic dihydropyridine treatment can reverse the behavioral consequences of and prevent adaptations to, chronic ethanol treatment, Br. J. Pharmacol. 103, 1669–1676.

    PubMed  Google Scholar 

  • Wilson, E. O., 1998: Consilience: The Unity of Knowledge, Random House, New York

    Google Scholar 

  • Wolgin, D. L., 1989: The role of instrumental learning in behavioral tolerance to drugs, in A. J. Goudie and M. W. Emmett-Oglesby (eds), Psychoactive Drugs: Tolerance and Sensitization, Humana, Clifton, NJ, pp. 17–114.

    Google Scholar 

  • Young, A. M. and Goudie, A. J., 1995: Adaptive processes regulating tolerance to the behavioral effects of drugs, in F. E. Bloom and D. J. Kupfer (eds), Psychopharmacology: The Fourth Generation of Progress, Raven Press, New York, pp. 733–742.

    Google Scholar 

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Authors and Affiliations

  1. Department of Human Development,Schiefelbusch Institute for Life Span Studies,Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas, U.S.A.

    Stephen C. Fowler

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Fowler, S.C. Behavioral Tolerance (Contingent Tolerance) isMediated in Part by Variations in Regional Cerebral Blood Flow. Brain and Mind 1, 45–57 (2000). https://doi.org/10.1023/A:1010098004889

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