Skip to main content
Log in

The effect of long-term treatment with deprenyl on basal and L-DOPA evoked dopamine release in vitro from the corpus striatum of aged rats

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

In the present experiment, male rats (15–17 months) were injected with deprenyl (0.25 mg/kg) three times per week for six months. At 21–23 months of age the male rats were sacrificed, the corpus striatum removed and superfused in vitro. Basal and evoked dopamine and DOPAC levels, as obtained with either two infusions of L-DOPA (L-DOPA/L-DOPA) or L-DOPA followed by amphetamine (L-DOPA/AMPH), were measured from effluent superfusion samples and compared with values obtained from similarly aged animals treated identically with saline and from that obtained with young (2–4 months) animals. Treatment with deprenyl resulted in significantly greater basal dopamine and significantly lower basal DOPAC output compared with basal release levels from saline-treated aged rats and young animals. Responses to L-DOPA/LDOPA or L-DOPA/AMPH evoked dopamine and DOPAC release did not differ between deprenyl and saline-treated aged rats, however, both groups showed a significantly reduced response profile to these stimulations (L-DOPA/ L-DOPA or L-DOPA/AMPH) compared to that of young rats. These results indicate that the selective Type-B monoamine oxidase inhibitor, deprenyl, exerts a basic change in dopamine metabolism within the corpus striatum of aged rats resulting in an increase of endogenous dopamine and a decrease in endogenous DOPAC output.

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

  • Birkmayer W, Birkmayer JGD (1989) The L-DOPA story. In: Calne DB, et al (eds) Parkinsonism and aging. Raven Press, New York, pp 1–7

    Google Scholar 

  • Brannan T, Bhardwaj A, Martinez-Tria J, Weinberger J, Yahr M (1990) Striatal L-DOPA metabolism studied in vivo in rats with nigrostriatal lesions. J Neural Transm [P-D Sect] 2: 15–22

    Google Scholar 

  • Cohen G, Spina MB (1989) Deprenyl suppresses the oxidant stress associated with increased dopamine turnover. Ann Neurol 26: 689–690

    Google Scholar 

  • Cohen G, Pasik P, Cohen B, Leist A, Mytilineous C, Yahr MD (1984) Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyrindine (MPTP) in monkeys. Eur J Pharmacol 106: 209–210

    Google Scholar 

  • DeGroot J (1959) The rat forebrain in stereotaxic coordinates. Verh K Ned Acad Wet [B] 2: 1

    Google Scholar 

  • Dluzen DE, McDermott JL, Ramirez VD (1989) The effect of L-DOPA upon in vitro dopamine release from the corpus striatum of young and old male rats. Exp Neurol 106: 259–264

    Google Scholar 

  • Dluzen DE, McDermott JL, Ramirez VD (1991) Changes in dopamine release in vitro from the corpus striatum of young versus aged rats as a function of infusion modes of L-DOPA, potassium and amphetamine. Exp Neurol (in press)

  • Dluzen DE, Ramirez VD (1986) In vivo release of dopamine and its metabolites following a direct infusion of L-DOPA into the caudate nucleus of awake, freely behaving rats using a push-pull cannula. Neurosci Lett 82: 29–34

    Google Scholar 

  • Georgi O, DeMontis G, Proceddu ML, Mele S, Calderini G, Toffano G, Biggio G (1987) Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum. Dev Brain Res 35: 283–290

    Google Scholar 

  • Haefely WE, Kettler R, Keller HH, DaPrada M (1990) Ro 19-6327, a reversible and highly selective monoamine oxidase β inhibitor: a novel tool to explore the MAO-β function in humans. In: Streifler MB, Korczyn AD, Melamed E, Youdim MBH (eds) Parkinson's disease: anatomy, pathology and therapy. Raven Press, New York, pp 505–512 (Adv Neurol 53)

    Google Scholar 

  • Henry JM, Filburn CR, Joseph JA, Roth GS (1986) Effect of aging on striatal dopamine receptor subtypes in Wistar rats. Neurobiol Aging 7: 357–361

    Google Scholar 

  • Knoll J (1983) Deprenyl (Selegiline): the history, its development and pharmacological action. Acta Neurol Scand [Suppl 95]: 57–80

    Google Scholar 

  • Knoll J (1985) The facilitation of dopaminergic activity in the aged brain by (−)deprenyl. A proposal for a strategy to improve the quality of life in senescence. Mech Aging Dev 30: 109–122

    Google Scholar 

  • Knoll J (1987) R-(−)-deprenyl (Selegiline, Movergan) facilitates the activity of the nigrostriatal dopaminergic neuron. J Neural Transm 25 [Suppl]: 45–66

    Google Scholar 

  • Knoll J (1988) The striatal dopamine dependency of life span in male rats. Longevity study with (−)deprenyl. Mech Aging Dev 46: 237–262

    Google Scholar 

  • Knoll J (1989) The pharmacology of selegiline ((−)deprenyl). New aspects. Acta Neurol Scand 126: 83–91

    Google Scholar 

  • Knoll J, Dallo J, Yen TT (1983) The long-lasting, true aphrodisiac effect of (−)deprenyl in sexually sluggish old male rats. In: Beckmann H, Riederer P (eds) Monoamine oxidase and its selective inhibitors. Karger, Basel, pp 135–153

    Google Scholar 

  • Langsten JW, Irwin I, Ricaurte GA (1987) Neurotoxins, parkinsonism and Parkinson's disease. Pharmacol Ther 32: 19–49

    Google Scholar 

  • Lees AJ (1987) Current controversies in the use of selegiline hydrochloride. J Neural Transm 25 [Suppl]: 157–162

    Google Scholar 

  • Missale C, Govoni S, Castelletti L, Spano PF, Trabucchi M (1983) Brain neurotransmitter changes in brains of aged rats. In: Agnoli A, Crepaldi G, Spano PF, Trabucchi M (eds) Aging brain and ergot alkaloids. Raven Press, New York, pp 15–22

    Google Scholar 

  • Morgan DG, May PC (1990) Age-related changes in synaptic neurochemistry. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging, 3rd edn. Academic Press, San Diego, pp 219–254

    Google Scholar 

  • Petkov VD, Petkov VV, Stancheva SL (1988) Age-related changes in brain neurotransmission. Gerontology 34: 14–21

    Google Scholar 

  • Ponzio F, Calderini G, Lomusco G, Vantini G, Toffano G, Algeri S (1982) Changes in monoamines and their metabolite levels in some regions of aged rats. Neurobiol Aging 3: 23–29

    Google Scholar 

  • Ramirez VD, Kim K, Dluzen DE (1985) Progesterone action on the LHRH and nigrostriatal dopamine neuronal systems. In vitro and in vivo studies. Rec Prog Horm Res 41: 421–472

    Google Scholar 

  • Riederer P, Youdim MBH, Birkmayer W, Jellinger K (1978) Monoamine oxidase activity during (−)deprenyl therapy: human brain post-mortem studies. In: Roberts PJ, Woodruff GN, Iversen LL (eds) Advances in biochemical psychopharmacology, vol 19. Raven Press, New York, pp 377–382

    Google Scholar 

  • Shoulson I, The Parkinson Study Group (1989) Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 321: 1364–1371

    Google Scholar 

  • Strong R (1988) Regionally selective manifestations of neostriatal aging. Ann N Y Acad Sci 515: 161–177

    Google Scholar 

  • Tetrud JW, Langston JW (1989) The effect of deprenyl (Selegiline) on the natural history of Parkinson's disease. Science 245: 519–522

    Google Scholar 

  • Watanabe H (1987a) Substrain differences of age-related changes in in vivo dopamine synthesis in the striatum and nucleus accumbens of the rat brain. J Pharmacobiodyn 10: 312–320

    Google Scholar 

  • Watanabe H (1987b) Differential decrease in the rate of dopamine synthesis in several dopaminergic neurons of aged rat brain. Exp Gerontol 22: 17–25

    Google Scholar 

  • Yahr MD (1987) R-(−)-deprenyl and parkinsonism. J Neural Transm 25 [Suppl]: 5–12

    Google Scholar 

  • Youdim MBH, Finberg JPM (1986) MAO Type B inhibitors as adjunct to L-DOPA therapy. In: Yahr MD, Bergmann KJ (eds) Advances in neurology, vol 45. Raven Press, New York, pp 127–136

    Google Scholar 

  • Youdim MBH, Riederer P (1986) MAO type B: its relation to MPTP induced and classical parkinsonism. In: Markey SP (ed) MPTP: a neurotoxin producing a parkinsonsim syndrome. Academic Press, New York, pp 203–218

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dluzen, D.E., McDermott, J.L. The effect of long-term treatment with deprenyl on basal and L-DOPA evoked dopamine release in vitro from the corpus striatum of aged rats. J. Neural Transmission 85, 145–156 (1991). https://doi.org/10.1007/BF01244706

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01244706

Keywords

Navigation