Effects of monoamino oxidase inhibitors on shuttle-box avoidance behaviour of hamsters

Pharmacological

Research Communications,

357

Vol. 4, No. 4. 1972

EFFECTS OF MONOAMINO OXIDASE INHIBITORS

ON SHUTTLE-BOX AVOIDAN-

CE BEHAVIOUR OF HAMSTERS. Mario Laboratory 1, via

of

Reno,

Received

00198

Rome,

1972

behaviour

Recently

overcome

by administration

(Sansone

and Renzi,

that

shuttle-box

ce training automated 24x21 (two tments

to

hamsters

played

and the

in

by brain

utility

of

evidentiate

test in

observed

responding of

1970,

the cate-

shuttlea psychosti-

evidentiate

the

present

antidepressant

the

low

findings

of

can be

of

suggest

hamsters

could

psychostimulant

action

research,

we have

studied

monoamine

oxidase

inhibitors,

iproniazid,

levels

or methylphenidate

The above behaviour

the

by hamsters

amphetamine

1971).

to

that

exhibited

avoidance

derivative,

METHODS

role

hamsters

we have

avoidance

tranylcypromine

the

of

and tra-

drugs.

shuttle-box

two

of

iproniazid

responding

behaviour

of

Thus,

inhibitors,

avoidance

INTRODUCTION

idrazine

Italy

confirm

in

a suitable

Renzi

The results

action

of

C.N.R.

avoidance

avoidance

fects

and Psychopharmacology,

, improved

cholamines

drugs.

Messeri

oxidase

shuttle-box.

the

and Patrizia

Two monoamine

nylcypromine

mulant

Paolo

Psychobiology

26 October

SUMMARY

-box

Sansone,

and a non

idrazine

the

be of efan

compound,

.

The technique of

hamsters

shuttle-boxes

cm compartments,

was the

same previously

(Sansone were

taken,

connected

10 W lamps)

was switched

and used

as conditioned

and Renzi, each

used 1970,

1971).

one divided

by a 7x7 cm opening. on alternately stimulus

in (CS).

for

the

into

avoidan. Eight two

A light two

compar-

The CS preceded

Pharmacological

358

the

onset

verlapped

of

the

unconditioned

it

for

45 sec.

discontinuously through

(0.5

a selenium

avoided

the

within

15 set

after

was 60 sec.

randomly

dance

(2.0 at

the

All

dose

promine

in

sion.

Table

five

50-trial

of

floor

was recorded

when the

dark

compartment

CS. The intertrial were

subjected

in

inter-

punished

and recor-

in

other

respectively. before

of

of

the

in

six

hamsters

improvement

very the

levels

of

in

experimental confirm

1971).

as sessions

second

expresses-

blocks

the

last

experimental

of

week). previous by low

acquisition

1970,

in

are

SO-trial

characterized

slowly only

groups

intraperito-

each

group

and Renzi,

in

dose

groups

avoidance

was evident

performance

each

are

shuttle-box

increased

the

for

control

saline

three

avoidances

for

avoi-

sessions.

avoidances

block

eight

and tranylcy-

experimental

mean percent

fact,

in

respectively,

ten

of

of

phosphate

the

were

SO-trial

administration

were

75

Friday).

injected

the

Sansone

to

Drugs

saline

that

daily

at

of

(one the

ten

consisting

two groups

each

1968;

the

the

between

The animals

group

Monday

iproniazid

the

weighing

to

20 and 40 mg/kg,

performance

in

each

consisted

sessions

However

grid

a 500.000

experiment.

(from

1 reports

and a sharp sion.

the

1 as mean percent

curve,

the

applied

through

hamsters

two weeks

10,

ka and Bunnel, ning

to

the

crossings

were

indicating

findings,

and o-

shock

V delivered

the

groups,

of

Performances

vels

six

one group,

hours

Fig.

off)

into of

of

Performances

RESULTS sed in

onset

in

5 and 10 mg/kg, four

(US) by 15 set

response

48 golden

to

sulfate

neally

set

(250

beginning

treatment

ml/kg) the

the

groups

sessions

Drug

1.5

US by running

were

assigned

subjects.

on,

Vol. 4, No. 4. 1972

responses.

The subjects and 95 g at

set

Spontaneous

ded as intertrial

Communications,

The US was an electric

A conditioned

animal

val

stimulus

rectifier

ohms resistance).

Research

le-

(Matal-

The learproceeded (10th)

ses-

week was

Pharmacological

Research Communications,

359

Vol. 4. No. 4. 1972

O1

2

3

4

,

t

1

I

I

5

0

7

8

9

1

10

SESSIONS

Fig.

1 - Mean percent avoidances in each of the ten daily SO-trial sessions. The experiment was carried out in two weeks, from Monday to Friday. C = control group (saline) ; IPZ 10, IPZ 20 and IPZ 40 = iproniazid phosphate at the doses of 10, 20 and 40 mg/kg respectively; TNP 5 and TNP 10 = tranylcypromine sulfate at the doses of 5 and 10 mg/kg respectively.

significantly

higher

The low

level

absence

of

at

of

to

responding

responses,

the

first

was not

which

on the

week

(Table

accompanied

contrary

were

1). by

always

a 100% level.

fective

at

proved dose

the

the

effects

dose

performances of

in

the

provements ble

comparison

avoidance

escape

As concerns

ly

in

1).

in

20 mg/kg, second

level

in

appeared

of

MAO inhibitors,

10 mg/kg,

comparison

fact,

week.

of

At

more

to

increased the evident

dose

iproniazid

while the

at

saline

avoidance level

of

higher

was inefdoses

control

group.

responding, 40 mg/kg

and statistically

im-

especial

avoidance significant

The

im(Ta-

360

Pharmacological

Research Communications,

Vol. 4. NO. 4, 1972

Mean percent avoidances (2 S.E.) in blocks of five SO-trial sessions. Significances betwegn drug and saline treatments were bssea on the Student t- test. IPZ = iproniazid

phosphate;

TNP = tranylcypromine

SESSIONS 1-5 Avoidances P Saline

6.8

-+ 1.8

IPZ

7.8

10 mg/kg

sulfate

SESSIONS 6-10 Avoidances P 28.7

-+ 6.8

-

)O.OS

23.4

)O.OS

>o.os

42.0

-+ 5.0 -+ 7.4

11 20 w/kg

14.0

-+ 2.0 + 3.7

40 w/kg

20.5

+ 2.8

(0.01

60.1

_+_3.4


5 mg/kg

17.1

+ 3.3

(0.05

47.3


10 mg/kg

28.6

+ 4.5

(0.001

67.2

-+ 4.1 + 4.9

TNP ”

x Differences significant xxP(O.05 for

between the two S-session in all groups. the ninth session.

Tranylcypromine the

dose

dance effect Table

level

of

responding was more

the

more

effective

drug

improved

comparison

evident

at

to

the

the

dose

were

of

statistically

iproniazid.

At

significantly

control level

(0.001

group.

of

avoiSuch an

10 mg/kg

(Fig.

1,

the

con-

1).

group,

(3-8%),

5 mg/kg in

Intertrial trol

appeared

blocks

;O.OSxx

but

DISCUSSION

under

responses, were

present

seldom

at

appeared

The facilitation

and tranylcypromine of

particular

interest

of

previous

researches

drug

treatments

some extent in

the

in

other

of

avoidance

observed

in

the

if

considered

concerning

the

the

first

two

sessions

sessions. responding

present in

as in

experiment,

comparison

effects

by iproniazid

of

with

appears the

MAO inhibitors

results

Pharmacological

Research Communications,

on avoidance avoidance

behaviour.

was depressed and Boff,

1960;

responding

has

(Moore

was instead

and Boff,

1971).

A facilitating

prolonged

activity

lower of

cating

the

that

fact,

brain

of the

behaviour

of

two

(Pletscher,

vious

data

Fuxe

Carlsson,

1963;

Finally,

that tle-box

can be explained is

the in 1967;

Seiden

a psychostimulant avoidance

of

the

the

two

and Herr,

to

the

of

subjected

behnviour

and Rech,

and Peterson

1967;

induced

can be easily of

indi-

1960).

on avoidance content

of

inhibition

catecholamines been

the

iproniazid

play

suggmsted

and Hanson,

experiment

action

in

findings

increased

has

at

Seiden

1966;

and

by iproniazid

support

the

evidentiated

an

by pre

1968).

improvements present

hamsters

and Erickson,

oxidase

brain

of

of

drugs

literature(Corrodi

Moore

behaviour

(Green

monoamine

levels

avoidance

effective

oxidase

by the the

or

alone

a difference

by the

much more

can be ascribed

That

given

in mice

Such

of

drugs

the

only

iproniazid.

produced

in

Voith

those

performance

tranylcypromine

1964;

1971)

on avoidance were

responding

hamsters

and Hanson,

and Herr,

avoidance

effect

reported

(Heise

improved

facilitating

in

tetrabenazine

(Oliverio,‘1967).

monoamine

role

behaviour

No effect

was observed

on

when avoidance

Voith

and Boff,

brain

1966).

MAO inhibitors

when MAO inhibitors

sessions

of

monoamines

important

1967).

tranylcypromine

as inhibitor In

and Rech,

effect

Tranylcypromine levels

1964;

Scheckel

avoidance

of

evidentiate

and Boff,

found

1960;

an effect

(Orsingher,l961),

Scheckel

(Heise

dose

been

by reserpine

c(-methyltyrosine

to

Generally

responding

361

Vol. 4. No. 4, 1972

and

assumption on shut-

hamsters.

REFERENCES Corrodi H. and Hanson L.C.F., Psychopharmacologia 10, 116-125, 1966, Fuxe K. and Hanson L.C.F., Psychopharmacologia 11, 439-447, 1967. Green H. and Erickson W., J. Pharmacol. exp. Ther. 129, 237-242, 1960.

362

Pharmacological

Research Communications,

Vol. 4. No, 4, 1972

Heise G.A. and Boff E., J. Pharmacol. exp. Ther., 129, 155-162, 1960. Matalka E.S. and Bunnel B.N., Psychon. Sci. 12, 27-28, 1968. Moore K.E. and Rech R.H., J. Pharmacol. exp. Ther., 156, 70-75, 1967. Oliverio A., 11 Farmaco (Ed. Sci.) 22, 159-171, 1967. Orsingher O.A.,Psychopharmacologia 2, 326-333, 1961. Pletscher A., Pharmacol. Rev. 18, 121-129, 1966 Sansone M. and Renzi P., Pharmacol. Res. Comm. 2, 355-360, 1970. Sansone M. and Renzi P., Pharmacol. Res. Comm. 3, 113-119, 1971. Scheckel C.L. and Boff E., Psychopharmacologia 5, 198-208,.1964. Seiden L.S. and Carlsson A., Psychopharmacologia 4, 418-423, 1963 Seiden L.S. and Peterson D.D., J. Pharmacol. exp. Ther. 159, 422-428, 1968. 20, 253-265, 1971. Voith K. and Herr F., Psychopharmacologia