Further observations on the effect of repeated electroconvulsive shock on the behavioural resposes of rats produced by increases in the functional activity of brain 5-hydroxytryptamine and dopamine

1 Rats were convulsed once daily for 7 days by exposure to the inhalant convulsant agent, flurothyl (Indoklon, bis (2,2,2-trifluouroethyl)ether). Twenty four hours after the final convulsion the rats were injected with tranylcypromine (20 mg/kg) followed 30 min later by L-DOPA (50 mg/kg), a procedure which increases brain dopamine concentrations. The flurothyl-treated rats showed a greater locomotor activity response than rats that had not been convulsed. 2 This enhanced response appears to be due to increased postsynaptic dopamine receptor sensitivity since flurothyl-treated rats also showed enhanced locomotor responses to methamphetamine (2 mg/kg) and apomorphine (2 mg/kg). 3 Enhanced 5-hydroxytryptamine-induced activity responses following administration of tranylcypromine (20 mg/kg) and L-tryptophan (50 mg/kg) were also seen 24 h after the last of 10 daily flurothylinduced convulsions. 4 The increased 5-hydroxytryptamine response also appears to be due to increased postsynaptic sensitivity since the flurothyl-treated rats showed increased hyperactivity following administration of tranylcypromine (20mg/kg) and the suggested 5-hydroxytryptamine agonist, 5-methoxy N,Ndimethyltryptamine (2 mg/kg). 5 No change in the brain concentration of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tryptophan, dopamine or noradrenaline was observed 24h after the last of 10 daily flurothyl-induced convulsions. compared to untreated rats. The rate of 5-hydroxytryptamine accumulation after tranylcypromine/L-tryptophan treatment and of dopamine and noradrenaline accumulation after tranylcypromine/L-DOPA treatment was similar in both groups. 6 Repeated flurothyl convulsion has the same effects on these behavioural tests as repeated electroconvulsive shock. Since both treatments have been used successfully to treat depression, it is suggested that the mechanism of action of electroconvulsive therapy may be by increasing postsynaptic responses to the monoamine neurotransmitters.

“…Due to the small amount of flurothyl available it was decided to try 7 daily treatments rather than 10 as in our previous studies (Evans et al, 1976;Green et al, 1977).…”

Section: Effect Of Repeatedflurothyl Convulsions On Tranylcypromineilmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Repeated Exposure of Rats to the Convulsant Agent Flurothyl Enhances 5‐hydroxytryptamine‐ and Dopamine‐mediated Behavioural Responses

Green

1978

“…There is now convincing evidence that repeated administration of electroconvulsive shock (ECS) to rats enhances the response in several 5-hydroxytryptamine-(5-HT)-mediated behavioural models (see, for example, Evans, Grahame-Smith, Green & Tordoff, 1976;Green Heal & Grahame-Smith, 1977; Green, Costain & Deakin, 1980; Lebrecht & Nowak, 1980).…”

Section: Introductionmentioning

confidence: 99%

Increased 5‐HT₂ receptor number in brain as a probable explanation for the enhanced 5‐hydroxytryptamine‐mediated behaviour following repeated electroconvulsive shock administration to rats

Green

Johnson

Nimgaonkar

1983

1 Following electroconvulsive shock (ECS) administration daily for 10 days there was an increase (35 %) in 5-hydroxytryptamine2 (5-HT2) receptor number in rat frontal cortex 24 h after the last ECS, compared with handled controls. A similar increase was seen after intermittent ECS administration (5 ECS over 10 days) given during halothane anaesthesia, compared with halothane-treated controls. The dissociation constant was also increased at this time. A single ECS had no effect. 2 Treatment of rats with pentylenetetrazol, p-chlorophenylalanine or a-methyl p-tyrosine during the intermittent ECS administration abolished the increase in 5-HT2 receptor binding. 3 Since enhanced 5-HT-mediated behavioural responses are seen after repeated ECS but not when the ECS is given with the drug treatments outlined above, it is suggested that ECS-induced enhancement of 5-HT-mediated behaviour results from an increase in 5-HT2 receptor number.

“…droxytryptamine (5-HT) agonists whilst mice show an Mice and rats also show an enhanced locomotor increased head-twitch response (Evans et al, 1976; response to dopamine agonists (Modigh, 1975;Evans Green et al, 1977;Lebrecht & Nowak 1980;Green et et al, 1976;Deakin et al, 1981) although there does al., 1983b). not appear to be any change in dopamine receptor number or dopamine-sensitive adenylate cyclase activity (Green et al, 1977;Bergstrom & Kellar, 1979; 'Correspondence Deakin et al, 1981).…”

Section: Repeated Administration Of Electroconvulsive Shockmentioning

confidence: 97%

Some anticonvulsant drugs alter monoamine‐mediated behaviour in mice in ways similar to electroconvulsive shock; implications for antidepressant therapy

Green¹,

Johnson²,

Mountford³

et al. 1985

1 The effects in mice of administration of the anticonvulsants, progabide, sodium valproate, diazepam, carbamazepine and phenytoin on 5-hydroxytryptophan (5-HTP)-induced head-twitch, apomorphine-induced locomotion, clonidine-induced sedation, and P-adrenoceptor and 5-HT2 receptor number have been examined. 2 Repeated progabide administration (400 mg kg-', i.p. twice daily for 14 days) enhanced the headtwitch response the effect lasting for over 8 days after the last dose, and also increased 5-HT2 receptor number in frontal cortex. 3 Progabide (400 mg kg-', i.p.) enhanced the head-twitch response when given once daily for 10 days and when given intermittently (5 times over 10 days) but not after 1 day of administration. 4 Repeated Na valproate (400mg kg-',i.p.) also increased the 5-HTP-induced head-twitch response and 5-HT2 receptor number in the frontal cortex when given twice daily for 14 days, but no behavioural enhancement was seen after 10 days' treatment. 5 Diazepam (1.25 mg kg-', i.p.) twice daily for 14 days increased the head-twitch response and 5-HT2 receptor number. 6 Repeated progabide and valproate (but not diazepam) administration attenuated the sedation response to the a2-adrenoceptor agonist, clonidine (0.15mg kg-') but neither drug altered 1-adrenoceptor number in the cerebral cortex. 7 No changes in apomorphine-induced locomotor behaviour were seen after progabide, valproate or diazepam.8 Repeated carbamazepine (20 mg kg-') or phenytoin (40 mg kg-1) administration failed to alter any of the biochemical or behavioural parameters listed above. 9 Like repeated electroconvulsive shock (ECS), progabide altered the head-twitch response, clonidine-induced sedation response and 5-HT2 receptor number. Unlike repeated ECS, it did not alter P-adrenoceptor number or the apormorphine-induced locomotor response. These data suggest that ECS may produce some changes in monoamine function by altering GABA metabolism as has previously been postulated.