INTERACTIONS OF QUININE AND SEROTONERGIC AGENTS IN PENTOBARBITONE - INDUCED SLEEP IN RATS

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Department of Medicine

ABSTRACT
The interactions between quinine serutuninergic agents on the EEG, EMG changes and behavioural sleep induced by pentobarbitone were studied in rats. All drugs were injected i ntr aper i tonealy. The sedative-hypnotic effect of pentobarbitone (5-30mg./kg) was found to be dependent on dose, with hypnosis being attained by the higher dose range (15-30mg/kg) . High dose (25mg/kg) of pentobarbitone synchronised the F C O C and BSRF of the control EEG in the slow wave sleep (SW3) stage with particular depression of the RF arid the EMG. When administered singly and in high doses (12-64mg/kg), 5- hydroxytryptophan (5-HTP) and quinine (5-50mg/kg) respectively showed sedative effects that were dose- dependent. High dose (20mg/kg) of Quinine sychronised the resting EEG and Initially briefly stimulated, though eventually predominantly depressed the EMG, suggesting a mechanism similar to that of the general CNS depressants. Low dose (0.1mg/kg) of quinine did not sedate but activated the entire resting state or control EEG and EMG. These were evident as faster, lower amplitude, asynchronous, mixed frequencies voltages and slightly increased multiple motor-unit voltages respectively. On sleep induced by pentobarbitone,5-Hydroxytryptophan 5-HTP (8-32mg/kg) and high doses (20-50mg/kg) of quinine respectively caused a potentiation that was marked by prolonged ix duration uT pentobarbitone-induced bleep. On the EEG and EMG patterns under pentobarbitone (25mg/kg), quinine 20mg/kg Increased the wave amplitude of the FC and OC with profound slowing of the BSRF and further reduction of muscle activity (muscle relaxation). Low doses (0.05 and 0.1 rug/kg) of quinine delayed the onset of sleep induced by pentobarbitone by 64% and 36% and shortened the duration respectively by 23% and 20%, the EEG arid EMG activities were also activited. A high dose (25mg/kg) of quinine potentiated 5-HTP-induced prolongation of pentobarbitone sleep by 23% while low dose (0.05mg/kg) of quinine decreased it by 40%. P-Chlorophenylalanine ((PCPA), 300mg/ky) reduced the duration of pentobarbitone sleep and antagonised the potentiation of pentobarbitone sleep by quinine. Ketanserin (2.5mg/kg) not only potentiated pentobarbitone sleep but enhanced significantly the potentiation of pentobarbitone sleep by 5-HTP (16mg/kg) as well as by quinine (25mg/kg). Methysergide (8mg/kg), an antagonist of both 5-HT1 , and 5- HT; receptors and a partial agonist of 5-HT, receptor partially antagonised the potentiating effect of high dose of quinine on pentobarbitone sleep. The present data show that depending on the dose, quinine has both excitatory and inhibitory effects on the state of condousness and that serotoninergic mechanism(s) may under the its effect on the state of sleep in rats.