Increased responsiveness to apomorphine after REM sleep deprivation: supersensitivity of dopamine receptors or increase in dopamine turnover? *

The behavioural effects of REM sleep deprivation in laboratory animals are characterized by increased responsiveness to external or internal stimuli (Cohen & Dement 1965; Dement 1965; Steiner & Ellman 1972; Jouvet 1977). Also, REM sleep-deprived rats show enhanced responses to apomorphine, bromocriptine and piribedil in aggressiveness, hypothermia and stereotyped behaviour (Tufik et al 1978; Tufik 1980). It has been suggested that the increased responsiveness following REM deprivation was the result of supersensitivity of postsynaptic dopaminergic receptors being brought about by the deprivation (Tufik et al1978). Other interpretations are also possible, as, for example. an augmentation of presynaptic dopaminergic activity. Ghosh et al(1976) reported that striatal dopamine levels were increased by 73 and 133% after 4 and 10 days of REM sleep deprivation, respectively. Therefore, the hyperresponsiveness of deprived rats to apomorphine after deprivation could merely reflect an excess of agonistic substances at the post-synaptic receptors, that is, injected apomorphine plus the larger amount of endogenous dopamine. The present report describes experiments to clarify this. Male albino Wistar rats, 3-4 months old, 250 to 350 g, were divided in 6 groups of 12 animals each, receiving the following treatments: groups I, I1 and I11 were normal (non-deprived) rats injected with, respectively, 50,100 and 200 mg kg-' of L-dopa; group IV had rats deprived of REM sleep for 96 h and which received 5 injections of vehicle scheduled as in group V; group V, were rats 96 h REM deprived and injected with 50 mg kg-I of a-methylp-tyrosine (AMPT) daily for 5 days (the injections starting immediately before REM deprivation, the last dose being administered 6 h before the end of deprivation period); group VI, were non-deprived animals treated with AMFT as above. L-Dopa and D,L-AMPT (Sigma Lab.) were suspended in distilled water with help of Tween-80; the injections were given intraperitoneally. REM deprivation was achieved by placing the rats on 6 cm platforms surrounded by water according to Alves et al (1973). Sixty min after injection of L-dopa and 6 h after the last dose of AMPT, which corresponded also to the end of REM deprivation period, all animals were injected i.p. with 5.0 mg kg-1 of freshly prepared apomorphine solution (Sigma Lab.). Pairs of identically treated animals were introduced into wire cages measuring 30 x 20 x 15 cm and the aggressive behaviour of each pair was scored in seconds for the following 30 min. Aggressive behaviour was defined as the time animals remained upright on their hindlegs, including when one animal forced its partner to assume different patterns of submissive postures. The results are summarized in the Fig. 1. Apomorphine failed to induce any sign of aggressive behaviour in the three groups of non-deprived rats previously treated with L-dopa; only typical stereotyped behaviour was noted in these animals. In the rats of group IV, deprived of REM sleep and injected with vehicle, apomorphine elicited 4158(701) s (mean with s.d.) of aggressive behaviour. confirming our previous finding (Tufik et al 1978). Finally, both groups pretreated with AMPT disclosed aggressive behaviour under apomorphine . These data argue strongly against the possibility that the hyperresponsiveness to apomorphine after REM deprivation is due to an enhanced amount of dopamine which would add its effects to the injected dopaminergic agonist. If this was so, rats given L-dopa pretreatment, which enhances dopamine in brain from 40 to 130% 1 h after its injection (Masur et al 1974), should behave