Skip to main content
Log in

Individual differences in dopamine release but not rotational behavior correlate with extracellular amphetamine levels in caudate putamen in unlesioned rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

It has been postulated that differences in pharmacokinetics do not contribute to the well-known individual variability in response to amphetamine (AMPH), but this is yet to be investigated thoroughly. Therefore, rotational behavior of outbred rats (Sprague-Dawley, 4 months old) was recorded during microdialysis sessions and striatal microdialysate was analyzed concomitantly for AMPH and dopamine concentrations after a single injection of 2.5 mg/kg AMPH SC. Three hours later these rats received three doses of 5 mg/kg AMPH SC (spaced 2 h apart) and their brain temperature was recorded every 20 min. The most important findings were: 1) the increase in extracellular dopamine was highly correlated with the corresponding peak AMPH levels in the microdialysate; 2) the peak dopamine level in response to 2.5 mg/kg AMPH was predictive of the hyperthermic response observed during 3 × 5 mg/kg AMPH and 3) high versus low rotators differed neither in their AMPH nor in their dopamine extracellular striatal concentrations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Askew BM (1962) Hyperpyrexia as a contributory factor in the toxicity of amphetamine to aggregated mice. Br J Pharmacol 19:245–257

    Google Scholar 

  • Baggot DJ, Davis LE, Neff CA (1972) Extent of plasma protein binding of amphetamine in different species. Biochem Pharmacol 21:1813–1816

    Google Scholar 

  • Bowyer JF, Holson RR (1995) Methamphetamine and amphetamine neurotoxicity. In: Chang LW, Dyer RS (eds) Handbook of neurotoxicology. Marcel Dekker, New York Basel Hong Kong, pp 845–870

    Google Scholar 

  • Bowyer JF, Gough B, Slikker Jr W, Lipe GW, NewPort GD, Holson RR (1993) Effects of a cold environment or age on methamphetamine-induced dopamine release in the caudate putamen of female rats. Pharmacol Biochem Behav 44:87–98

    Google Scholar 

  • Bowyer JF, Clausing P, Newport GD (1995) Determination ofd-amphetamine in biological samples using high-performance liquid chromatography after precolumn derivatization witho-phthaldialdehyde and 3-mercaptopropionic acid. J Chromatogr B 666:241–250

    Google Scholar 

  • Brodie BB, Cho AK, Gessa GL (1970) Possible role ofp-hydroxynorephedrine in the depletion of norepinephrine induced byd-amphetamine and in tolerance to this drug. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press, New York, p 270

    Google Scholar 

  • Camp DM, Robinson TE (1994) Amphetamine and cocaine pharmacokinetics in Lewis and Fischer 344 rats. Soc Neurosci Abstr 20:830

    Google Scholar 

  • Chance MRA (1947) Factors influencing the toxicity of sympathomimetic amines in solitary mice. J Pharmacol Exper Ther 89:289–296

    Google Scholar 

  • Cho AK, Kumagai Y (1994) Metabolism of amphetamine and other arylisopropylamines. In: Cho AK, Segal DS (eds) Amphetamine and its analogs. Psychopharmacology, toxicology, and abuse. Academic Press, San Diego New York Boston London Sidney Tokyo Toronto, pp 43–76

    Google Scholar 

  • Clausing P, Ferguson SA, Bowyer J (1995a) Individual differences in response to amphetamine. Soc Neurosci Abstr 21:972

    Google Scholar 

  • Clausing P, Gough B, Holson RR, Slikker Jr W, Bowyer JF (1995b) Amphetamine levels in brain microdialysate, caudate putamen, substantia nigra and plasma after dosage that produces either behavioral or neurotoxic effects. J Pharmacol Exp Ther 274:614–621

    Google Scholar 

  • Crowne DP, Tokrud PA, Brown P (1992) Relation of rotation to egocentric and allocentric spatial learning in the rat. Pharmacol Biochem Behav 43:1151–1153

    Google Scholar 

  • Davis JM, Kopin IJ, Lemberger L, Axelrod J (1971) Effects of urinary pH on amphetamine metabolism. Ann NY Acad Sci 179:493–501

    Google Scholar 

  • Dring LG, Smith RL, Williams RT (1970) The metabolic fate of amphetamine in man and other species. Biochem J 116:425–435

    Google Scholar 

  • Glick SD, Jerussi TP, Fleisher LN (1976) Turning in circles: the neuropharmacology of rotation. Life Sci 18:889–896

    Google Scholar 

  • Gonzalez FJ (1990) Molecular genetics of the P-450 superfamily. Pharmacol Ther 45:1–38

    Google Scholar 

  • Holson RR, Bowyer JF, Clausing P, Gough B (1996) Methamphetamine-stimulated striatal dopamine release declines rapidly over time following microdialysis probe insertion. Brain Res (in press)

  • Honecker H, Coper H (1975) Kinetics and metabolism of amphetamine in the brain of rats of different ages. Naunyn-Schmiedeberg's Arch Pharmacol 291:111–121

    Google Scholar 

  • Hooks MS, Jones GH, Neill DB, Justice Jr JB (1991) Individual differences in amphetamine sensitization: dose-dependent effects. Pharmacol Biochem Behav 41:203–210

    Google Scholar 

  • Hooks MS, Jones GH, Liem BJ, Justice Jr JB (1992) Sensitization and individual differences to ip amphetamine, cocaine, or caffeine following repeated intracranial amphetamine infusions. Pharmacol Biochem Behav 43:815–823

    Google Scholar 

  • Jerussi TP, Glick SD (1974) Amphetamine-induced rotation in rats without lesions. Neuropharmacology 13:283–286

    Google Scholar 

  • Jori A, Caccia S, Guiso G, Garattini S (1978) Distribution and localization ofp-hydroxy-d-amphetamine in rat brain. Eur J Pharmacol 52:361–365

    Google Scholar 

  • Koshikawa N (1994) Role of the nucleus accumbens and the striatum in the production of turning behaviour in intact rats. Rev Neurosci 5:331–346

    Google Scholar 

  • Kuczenski R, Segal DS (1994) Neurochemistry of amphetamine. In: Cho AK, Segal DS (eds) Amphetamine and its analogs, Psychopharmacology, toxicology, and abuse. Academic Press, San Diego New York Boston London Sidney Tokyo Toronto, pp 81–113

    Google Scholar 

  • Kurashima M, Yamada K, Nagashima M, Shirakawa K, Furukawa T (1995) Effects of putative dopamine D-3 receptor agonists, 7-OH-DPAT, and quinpirole on yawning, stereotypy and body temperature in rats. Pharmacol Biochem Behav 52:503–508

    Google Scholar 

  • Lokiec F, Rapin JR, Jacquot, Cohen Y (1978) A comparison of the kinetics ofd- andl-amphetamine in the brain of isolated and aggregated rats. Psychopharmacology 58:73–77

    Google Scholar 

  • Marona-Lewicka D, Vetulani J (1988) Stability and variability of locomotor responses of laboratory rodents. IV. The responses of rats and mice to apomorphine and amphetamine. Pol J Pharmacol Pharm 40:281–294

    Google Scholar 

  • McLellan-Green P, Waxman DJ, Caveness M, Goldstein JA (1987) Phenotypic differences in expression of cytochrome P-450g but not its mRNA in outbred male Sprague-Dawley rats. Arch Biochem Biophys 253:13–25

    Google Scholar 

  • Nagashima M, Yamada K, Kimura H, Matsumoto S, Furukawa T (1992) Hyperthermia induced by the dopamine D1 receptor agonist SK&F38393 in combination with the dopamine D2 receptor agonist talipexole in the rat. Pharmacol Biochem Behav 43:993–997

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, New York

    Google Scholar 

  • Pardridge WM, Connor JD (1973) Saturable transport of amphetamine across the blood-brain barrier. Experientia 29:302–304

    Google Scholar 

  • Rockhold RW, Carver ES, Ishizuka Y, Hoskins B, Ho IK (1991) Dopamine receptors mediate cocaine-induced temperature responses in spontaneously hypertensive and Wistar-Kyoto rats. Pharmacol Biochem Behav 40:157–162

    Google Scholar 

  • Segal DS, Kuczenski R (1987) Individual differences in responsiveness to single and repeated amphetamine adminsitration: behavioral characteristics and neurochemical correlates. J Pharmacol Exp Ther 242:917–926

    Google Scholar 

  • Segal DS, Kuczenski R (1994) Behavioral pharmacology of amphetamine. In: Cho AK, Segal DS (eds) Amphetamine and its analogs. Psychopharmacology, toxicology, and abuse. Academic Press, San Diego New York Boston London Sidney Tokyo Toronto, pp 115–150

    Google Scholar 

  • Seiden LS, Sabol KE, Ricaurte GA (1993) Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharm Tox 33:639–677

    Google Scholar 

  • Tallarida RJ, Murray RB (1986) Manual of pharmacologic calculations with computer programs, 2nd edn. Springer, New York Berlin Heidelberg London Paris Tokyo

    Google Scholar 

  • Ungerstedt U (1971) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behavior. Acta Physiol Scand Suppl 367:49–68

    Google Scholar 

  • Ungerstedt U (1984) Measurement of neurotransmitter release by intracranial dialysis. In: Marsden CA (ed) Measurement of neurotransmitter release in vivo. Wiley, New York, pp 81–105

    Google Scholar 

  • Verma A, Kulkarni SK (1993) Differential role of dopamine receptor subtypes in thermoregulation and stereotypic behavior in naive and reserpinized rats. Arch Int Pharmacodyn Ther 324:17–32

    Google Scholar 

  • Willar CD, Crowne, DP (1989) Circling, hemispheric asymmetry, and left-right discrimination. Brain Res 500:405–407

    Google Scholar 

  • Yehuda S, Kahn M (1977)d-Amphetamine thermal effects, metabolic rate and motor activity in rats. Int J Neurosci 7:207–210

    Google Scholar 

  • Zarrindast MR, Tabatabai SA (1992) Involvement of dopamine receptor subtypes in mouse thermoregulation. Psychopharmacology 107:341–346

    Google Scholar 

  • Zimmerberg B, Glick SD, Jerussi TP (1974) Neurochemical correlate of a spatial preference in rats. Science 185:623–625

    Google Scholar 

  • Zimmerberg B, Strumpf AJ, Glick SD (1978) Cerebal asymmetry and left-right discrimination. Brain Res 140:194–196

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clausing, P., Bloom, D., Newport, G.D. et al. Individual differences in dopamine release but not rotational behavior correlate with extracellular amphetamine levels in caudate putamen in unlesioned rats. Psychopharmacology 127, 187–194 (1996). https://doi.org/10.1007/BF02246126

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246126

Key words

Navigation