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Brain tyrosine depletion attenuates haloperidol-induced striatal dopamine release in vivo and augments haloperidol-induced catalepsy in the rat

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Abstract

Rationale

There are conflicting reports as to whether alterations in tyrosine levels affect functional indices of striatal dopamine (DA) transmission. Since the DA antagonist haloperidol (HAL) increases striatal DA release and induces catalepsy through its actions on striatal DA systems, it provides a useful paradigm to assess both neurochemical and behavioral effects of lowering brain tyrosine levels.

Objectives

To determine how brain tyrosine depletion affects HAL-induced catalepsy and striatal DA release in awake, freely moving rats.

Methods

In male rats, a control or tyrosine- and phenylalanine-free neutral amino acid solution NAA(−) (IP) was administered 30–60 min prior to HAL (IP). In one cohort, striatal microdialysate was assayed for DA levels. In a parallel cohort, catalepsy was measured using the bar test.

Results

NAA (−) reduced striatal tyrosine levels by 60%. The latter did not affect basal striatal DA release, but consistently delayed the attainment of maximal HAL-induced (0.19 mg/kg and 0.25 mg/kg SC) striatal DA release; the latter was abolished by administration of tyrosine. NAA(−) also potentiated HAL-induced catalepsy.

Conclusions

Acute brain tyrosine depletion attenuates HAL-induced striatal DA release and potentiates haloperidol-induced catalepsy. Both effects can be reversed by administration of tyrosine. Overall, the data indicate that tyrosine depletion affects both neurochemical and behavioral indices of striatal DA release.

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Acknowledgements

The authors thank Dr. Bryan Yamamoto for his technical consultation. This research was supported by the Office of Research and Development, Medical Research Service of the Department of Veterans Affairs. Dr. Jaskiw has conducted clinical trials for and/or received lecture sponsorship from the following: Bristol-Myers, Janssen, Lilly, Novartis, Pfizer, Zeneca Inc.

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Authors and Affiliations

  1. Psychiatry Service 116A(B), Louis Stokes Cleveland VAMC, 10000 Brecksville Road, Brecksville, OH, 44141, USA

    George E. Jaskiw & Rodolfo Bongiovanni

  2. Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA

    George E. Jaskiw

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  1. George E. Jaskiw
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  2. Rodolfo Bongiovanni
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Correspondence to George E. Jaskiw.

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Jaskiw, G.E., Bongiovanni, R. Brain tyrosine depletion attenuates haloperidol-induced striatal dopamine release in vivo and augments haloperidol-induced catalepsy in the rat. Psychopharmacology 172, 100–107 (2004). https://doi.org/10.1007/s00213-003-1619-3

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  • DOI: https://doi.org/10.1007/s00213-003-1619-3

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