Behavioural, ECoG and neuropathological effects after intracerebral injection of MPP+ and paraquat in rats

Pharmacological Resear ch, Vol. 21, Supplement 1, 1989

45

BEHAVIOURAL, ECoG AND NEUROPATHOLOGICAL EFFECTS AFTER INTRACEREBRAL INJECTION OF MPP+ AND PARAQUAT IN RATS Iannone M., CalO M., Rispoli V. and NisticO G. Institute of Pharmacology, Faculty of Medicine Catanzaro, University of Reggio Calabria, Italy. Key words: paraquat, MPP+, behaviour, neuropathology, ECoG MPTP (1-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine) produces in man,

monkeys,

neurochemical (1) .

marmosets lesions

mice

resembling

e

neuropathological of

Parkinson's

MPP+

(1-methyl-4-phenyl-pyperidiniurn

accumulation of MPP+ the substantia paraquat,

a

(2).

widely used herbicide, has and

neuropathological

the The

selectively in the dopaminergic neurons of

nigra produces a degeneration of these

MPTP

of MPP+ and

ion)

and

disease

MPTP is not itself toxic but is converted by MAO-B to

charged

with

and

its

chemical

metabolites . .. We

have

neurons.

similarities studied

the

and behavioural effects of the micro injection

paraquat into several areas of the rat brain .

Adult Wistar Morini rats (200-250 g) were stereotaxically implanted with stainless steel guide cannulae, under chloral

hydrate

anaesthesiam according to the atlas coordinates of Paxinos Watson (1982) into some areas of the rat brain.

and

Electrocortical

(ECoG) activity was recorded by means of an 8 channel EEG machine (OTE Biomedicam Florence). For the histological study the rat was perfused intracardiacally with a fixing solution (4% buffered paraphormaldehyde pH 7.4), the brain removed and treated with routine

techniques

to obtain paraffin embedded 10 urn

thin

slides

that were stained with Nissl method. 1043-6618 /89/2110045~2/$03 .00/0

© 1989 The Italian Pharmacological Society

46

Pharmacological Research. Vol. 21. Supplement 1,1989

The

microinfusion of paraquat (3.2,16,32,160 rumo1) into the

s.nigra

pars

deviation, ECoG

compacta

produced

contralateral

head

and

behavioural and motor stimulation, associated

desynchronization

and

with

voltage

high

spike

discharges.Paraquat infused, at the same doses, into the coeruleus

or

circling,

escape

into

the raphe

nuclei

responses, jumping

produced and

and

epileptic

phenomena. The

infusion of MPP+ at the same doses

produced

changes.

The

behavioural

micro injection of MPP+

all

the

prominent More

areas

desyncronization

similar but less marked and

at the higher

studied

proliferative

with

in

the

same

behavioural

and

ECoG

to

the

phenomena

ECoG

contralateral convulsions

by

ECoG

locus

clonic

accompanied

areas

neck

due

doses were associated

in

accompanied

by

neuronal

loss

vascular changes and

massive

marked neuropathological findings were observed

gliosis. after

the

microinjection of equimolar doses of paraquat. A

particular

feature

was the selective

vulnerability

of

the

hippocampal CA3 neurons observed 5-8 days after microinfusion

of

paraquat (1.6 nmol) into the substantia nigra, pars compacta

or

into the ventral tegmental area. REFERENCES 1) Jenner P., Rupniak N.M.J., Rose S., Kelly E., Kilpatrick G., Lees A. and Marsden C.D. l-methyl-4-phenyl-1,2,3,6-tetrahydropiridine induced parkinsonism in the common marmoset. Neurosci. Lett. 1984; 50: 85-90. 2)

Langston J.W. MPTP and Parkinson disease,i. TINS 1985; 8: 79-83.