Summary
A single dose of L-3,4-dihydroxyphenylalanine (l-DOPA, 100 mg/kg i.p.), after peripheral DOPA-decarboxylase inhibition by means of N1-(DL-seryl)-N2-(2,3,4-trihydroxybenzyl) hydrazine (Ro 4-4602, 50 mg/kg i.p.) given to reserpinepretreated (5 mg/kg i.p.) male rats, was found to reverse the reserpine-induced suppression of a conditioned avoidance response (CAR). This reversal followed the same time course as the increase in central dopamine (DA) levels, whereas the small but significant increase in central noradrenaline (NA) levels had a longer duration than the CAR reversal. When L-DOPA was given to rats pretreated with reserpine and bis-(4-metliyl-l-homopiperazinylthiocarbonyl)disulfide (FLA-63, 10 mg/kg i.p.), a DA-Β-hydroxylase inhibitor, the accumulation of NA was inhibited and the CAR reversal was markedly reduced. Animals treated with FLA-63 in addition to reserpine displayed a more stereotyped behaviour after L-DOPA than those not treated with FLA-63 and it is suggested that NA has a moderating influence on sterotyped behaviour. The results obtained in the current investigation provide further support for the view that the loss of CA, especially, DA, is of importance for the gross behavioural syndrome observed after reserpine. It is suggested that DA is important for elementary motor functions (e.g. locomotor activity) whilst additional NA receptor stimulation is essential for more complex and integrated behaviour (e.g. a conditioned avoidance response).
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This work was supported by grants from the Swedish Medical Research Council (B72-14X-155-08A; B 72-14X-502-08A); Faculty of Social Sciences and the Faculty of Medicine, University of Gothenburg; “Stiftelsen Wilhelm och Martina Lundgrens Vetenskapsfond”; “Svenska SÄllskapet för Medicinsk Forskning” and “överlÄkare Albert Wallins Fond”. For a generous supply of drugs we thank Dr. A. Pletscher, Hoffmann La Roche, Basel (Ro 4-4602); Astra, SödertÄlje (FLA-63) and Swedish CIBA, Stockholm (reserpine). The skilful technical assistance by Mrs. Ulla Axelsson and Mrs. Inger Oscarsson and the preparation of the figure by Research Engineer Tor Magnusson is greatfuIly acknowledged.
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Ahlenius, S., Engel, J. Behavioural and biochemical effects of L-DOPA after inhibition of dopamine-Β-hydroxylase in reserpine pretreated rats. Naunyn-Schmiedebergs Arch. Pharmak. 270, 349–360 (1971). https://doi.org/10.1007/BF01002347
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DOI: https://doi.org/10.1007/BF01002347