The transition from a fixed ratio to a fixed interval schedule of reinforcement in hypo and hyperthyroid rats

Pharmacological

Research

Communications.

THE TRANSITION

Vol. 17, No. 5, 1985

FROM A FIXED

463

RATIO TO A FIXED

INTERVAL

SCHEDULE

OF REINFORCEMFNT IN HYPO AND HYPERTHYROID RATS.

Fundarb

A.,

Molinengo

Institute

of

L.

and Cassone

Pharmacology

C. Raffaello

M.C.

and Pharmacognosy

31 - 10125

Turin

Received

- School

of

Pharmacy

- Italy in final form

6 March

1985

SU"IMARY The modification

of

behavior

roidism

were

studied

when

the

changed

from

a fixed

ratio

to

The conditions with

of hypo

a chronic

xine.

of

the

determined

by evaluation

the

levels

of

Hyperthyroidism

(learning) in

high

sion

of

the

the

a fixed

in

behaviour

learning

were

of basal

and of

thyroid

obtained 1-thyro=

activity

metabolic

rate

was and of

T4. no modification to

the

In

of

the

rat

new experimental

hypothyroidism.

hypothyroidism. rat

the

was

interval.

modifications of

and hyperthy=

reinforcement

of methimazole

adapting

was found

dent

of

in

of

and hyperthyroidism

caused

A difficulty

by hypo

schedule

administration

The level

plasma

caused

This

low

situation

effect

is

hypothyroidism

may interfere

with

behaviour.

evi=

a depres=

the

modification

process.

INTRODUCTION The thyroid heimer

et

protein reported hydroxylase Singhal

hormones

al.

,1974)

synthesis that

can enter

and influence

(Verity

et

hypothyroidism activity

(1976)

0031-6989/85/050463-08/$03.00/0

observed

in

al.

mature

an increase

mature

the

aminoacid

,1977).

caused the

the

brain

Emlen

an elevation brain of

uptake

0 1985

and

and others(1972) of

and Rastogi tyrosine

(Oppen=

tyrosin= and

and trypto=

The

Italian

Pharmacological

Society

464

Pharmacological

phan

in

the

Moreover

of

Hoffman

offered the

brain

of

cholinergic thyroid

1974). actions

contrast

of

dence

of

thyroid

the

et

evident in

the

dramatic,

man (Whybrow

and Ferrel and clinical

subjects,

adult

the

often

neurochemical

adult

animals of

with

Finally,an

there

is

evi=

there

is

no

thyroidectomy

reviews

of Eayrs,

may be a consequence

of

the

actions

We now report

darb

adult

(1981)

hormones

system.

in

(see

inconsistencies

ascertain

with

nervous

as a result

hormones

sensitivity

rats

thyroid

evident,

in

behaviour

of

the

l-triiodothyronine.

and others

causes

hormones that

with

Vol. 17, No. 5, 1985

or of 1960

and of

and Oppenheimer,l979).

These cient

the

these

suggests

modification

Schwartz

to

thyroid

which

giving

iunction

Communications,

(1947),Baruch

of

modifications

In

treated

an interaction

section

behavioural

rats

and others

evidence

abnormal

adult

Research

of

the

al .,1983)

behavioural

methods

the

hormones.

thyroid

results

a behavioural

of

obtained

test

exhibited

in

which

in

an insuffi=

utilized

hypo

and hyperthyroid

previous

a considerable

to

researches

(Fun=

sensitivity.

METHODS Twenty used.

iive

male

The animals,

experiments,were about

20°C)

with

The single was used dule

lasted

morning

for

lo-12

saltz

weighing

200-250

kept

in

food

and water

lever

and all

the

the

rats(Wistar

groups other

for hours of four

groups

Skinner

the

rats

(1 reinforcement

session

five

albino

every

15 minutes.

were

in

were

beginning

cages

of

ad libitum. rats

trained

of to

the

Grason

&Stadler

ratio

sche=

a fixed on the

lever).

Each

were

performed

kept

without

before

the

trials.

Rats

were

The rats

one group a solution

Serva-Feinbiochemica,Heidelberg)

the

(temperature

The experiments week.

drank

five

strain)

the

10 responses

per

groups

g at

box for

5 days

5 animals:

of

derived

drank of

were water

food

divided

in

(controls),

l-thyroxine

2mg/liter

in

(Naor

l-thyro=

Pharmacological

xine

Research

Communications,

4 mg/liter

mazole

or of

drank

about

about

28 ml/day/rat.

After of

The rats

35 ml/day/rat.

20 davs

of

reinforcement

interval

schedule:

bolic

after

rate

et

was used.Oxygen

fixed

for

of

to

the

first

first

to

vein

of

immunosorbant

The procedure

the

meta=

method

given

S.p.A.,Milan)

in

small

animals

was transformed of in

the

D'Amour

in et

a1.(19691

a few ml of

rat.

assay,

suggested

5 min

100 minutes.

(Terzano

minute

determined

after

The basal

consumption

were

a fixed

was evaluated

according

indications

less,

schedule

to

lasted

trials.

the

drank

given

trials

per

groups

the time

response

oxygen

caudal

T4 (Enzym urn linked

the

The apparatus

T4 levels

from

treatment,

interval

consumption

The serum

was used.

groups

was measured

according

collected

The methimazole

and hyperthyroidism

determination

cal/sqm/hr

l-thyroxine

interval

a1.(1969).

or of methi=

two

the

the

(BVR)

by D'Amour the

only

of hypo

immediately

the

pharmacological

The fixed

The level

250 mg/liter

of

was changed

was reinforced.

for

methimazole

500 mg/liter.

465

Vol. 17, No. 5, 1985

blood (R)

The Enzymum-Test

Boehringer,Mannheim)

by the

above

firm

of

the

controls

with

low

was

followed. RFSULTS The basal 0.83

In

cal/sqm/hr.

l-thyroxine

the

drinking to

metabolic

the

methimazole

induced

low

doses

a reduction

test

indicates

doses

( ~40.01 not

of

significant

of

doses

of

and in

l-thyroxine

and high the

was 59.16+_

it

the

rats

increased

concentrations

BMR respectively

of to

cal/sqm/hr. that

l-thyroxine

),while

cal/sqm/hr of

The low

47.19k1.40

are

treated

concentration

and to

by high

significant

rats

cal/sqm/hr.

The Student's

(BMR)

BMR was 61.00+0.54

caused

49.85k2.65

the

higher

64.57+1.03

rate

the

the

metabolism or of

methimazole

BMR modifications

( p > 10% >.

modifications are caused

by

466

Pharmacological

The T4 level increased

the

rats

high

were

respectively

T41evels

The differences highly

between

significant

On the and the fixed

number

ratio

luation

or low

to the

of the

results

These last

20 minutes

experimental the first

number

bability

of

controls

and treated

ber

a casual

cent

differences

were

animals. N20'

ces between

reported controls

values

indicate

in

number

centages increased.

of the

per

by Skinner(l938).

animal

and in

of the C-T

between

by rats

trials

(C)

the

differences

in

the

and in

(T),were

to estimate

the

various

given

administration

(P)

eva=

20 minutes

control

the

of responses

differences?.100

was used

from

cal= pro=

between

- NlOO' ,100 between the num= N20' during the 100 minutes of expe=

calculated.

The results

the

first each

in

test

result

always

and by treated

quantitative

suggested

for

drug

of responses/reinforcement

riment

method

made in the

after

were

was changed

per reinforcement

The Mann-Whitney

rats

the

of experiment trials

~g/lOOml.

of reinforcements

by control

The per cent

culated.

The per

number

we measured

of responses

corresponding

groups

the

of experiment

20 minutes

and 1.85kO.15

For

were

groups.

number

the

given

the

measurements

of methimazole

interval.

reinforcement,following

rats

).

of reinforcements

fixed

the

of l-thyroxine.

and treated

measured

of responses

ml and it

ml in

concentrations

controls

schedule

pg/lOO

1.25+0.17

Vol. 17. No. 5, 1985

pg/lOO

or 4mgfliter

( p < 0.01

tracings,we

when the

18.05+0.40

2mg/liter

drinking

Communications,

was 2.7OkO.20

and to

respectively

In the

rats

controls

to 6.4050.25

drinking the

in

Research

indicate

in

table

and treated

that

drug

1 are the rats.

administration

per

Therefore caused

of responses/reinforcement,while that

A statistically

the

number significant

cent

differen=

positive a reduction negative

per=

of responses/reinforcement reduction

of the

re=

Pharmacological

Table

Research

Communications,

1 - Differences

treated

between

rats(n*=number

forcement

given

interval

in

schedule.

estimated

with

controls(nl=number

of items) the

first

in

the

20minutes

The probability

the

467

Vol. 17, No. 5, 1985

number

items)

interval

in

the

fixed

result

(P) was

test.

Per cent differences

nl

n2

P

Low hypothyroidism

+66.60

5

5

0.008

High

hypothyroidism

- 9.34

5

5

0.421

Low hyperthyroidism

+ 5.63

5

5

0.50

High

-39.93

5

5

0.111

Table

hyperthyroidism

2 - Differences

cement

given

in

last

the

in

with

first

the number

The probability the

Mann-Whitney

Treatment

of responses/reinfor=

20 minutes(nl=number

20 minutes(n2=number

xed interval. mated

the

between

of

of of the

items)

of a casual

result

items)

and

trial

at fi

(P) was estL

test.

Per cent differences

nl

n2

P

Controls

+82.76

5

5

0.004

Low hypothyroidism

+47.28

5

5

0.075

High

hypothyroidism

+58.30

5

5

0.111

Low hyperthyroidism

+7a.53

5

5

0.048

High

+87.42

5

5

0.004

hyperthyroidism

and

of responses/rein

of a casual

Mann-Whitney

Treatment

of

468

Pharmacological

soonsesfreinforcement observed

only

in

in

the

hypothyroidism. is

In

The data ween the min

and

reported

the

the

per

last

the

other

and

reduction

hypothyroid

responses/reinforcement

of

experiment

but

condition

in

to

trial

in

the

hyperthyroid

of

the

responses is

the

which

the

differences

first

20 schedule

schedule.

rats

there

is

a con=

reinforcement.

first

of

to

are

bet=

the

some reduction

from

there

controls.

interval

per

low

differences in

in

a fixed

of

the

cent

given

the

was

situations to

per

reinforcement

these

the

Vol. 17, No. 5, 1985

experiment

experimental

2 are

groups,there

of

in

difference

table

20 min

Communications,

20 min of

rats

was changed

controls

siderable

of

the

in

responses in

first

significant

of reinforcement In

group

all

no statistically

the

Research

not

the

In

the

number

last

20 min

statistically

significant.

DISCUSSION The evaluation indicate

that

obtain two

the

BMR and of

conditions the

schedule

transition

to

of

pharmacological

pressive the

(table action

the

cement comparing

which

the data

limit

of

by the

table

and high)

a fixed

to reduce

the

of

1 response

rate in

with

number

rat of

20 min

the

2 to

the

of

of

responses

reduction

in per

determi= reinfor=

may be evaluated data

a de=

of reinforcement.

behaviour

experiment

five

caused

first

new schedule the

and

interval

the

as an evaluation

interfere

100 min of of

to

of

in

be taken

the

us to

responses/reinforcement

might

caused

reduction

the

has

treatment

of a depression

during

the

the

l),may

responses

The weight

ratio

rat

T4

and high).

a fixed

a theoretical

A reduction

experiment

ning

from

(low

(low

of

allowed

hyperthyroidism

reinforcement

of responding

by the

of

concentrations

treatment

of hypothyroidism

of

minutes.

plasma

pharmacological

two conditions

In

of

of

of

table

1.

Pharmacological

Research

There the

is

in

reduction

not

in

beginning

differ

from that

rat

to

On the

in

the

the to

that

in is

of

the

fixed

the

rats

20 min

in

of

the

rat

there the

to

thyroidism

defines

this

in

interfere

may be noted

of

the

have

which

the

necessitate different behavioural

by the the

of

is

of adapting of

the

20 minutes

in

not

the in

case

the

in

first

no indication

of

data

2 in=

of

of

table

these

rats

a

in

reinforcement. as the to

process

adjust

that damage

the in

doubts

of

the

rat

low the

hype=

to

for

situation

for

only

room

depression

between

by means

to new situations.

causes leaves

found

hype=

reduction

last

is

experimental

been

(Cassone

difficulty

and the

differences

low

depression

we may conclude

effect

also

This

hypothyroidism:

able

This

the

number

This

hyperthyroidism

in that

decay

obtaining

becomes

and not

hypothyroidism

which

of responses

learning

definition

process.

memory

the

2).

of

of

situation.

difficulty

new schedule

ability

of

1) there

evident

the

of

in

high

results

conditions

the

behaviour

is

These

2) does

in

shown

(table

an animal

According

thyroidism

of

l).The

(table

modify

experiment.

(table

(table

experiment

controls.

determine

trial

Kreezer(l971)

might

rats

situation

experiment

to

learning

the

the

and

responses/reinforcement

does not

of

conditions

that

of which

in

the

might

interval

depression

adapting

end of

rats

experiment

the

responses/reinforcement

of

dicate

of

a reduction

experimental

of

hyperthyroid

new experimenta.

20 minutes

behaviour

number

the

the

contrary,

first

the

rats

found

to

the

20 min

hyperthyroidism

there

rat

first

to

adapt

thyroidism

between

hyperthyroid

the

indicate the

the

469

Vol. 17, No. 5, 1985

no difference

controls

from

Communications,

low

behaviour

we used.

It

and high

hype=

modifications

of

and Molinengo,l981).

These

an explanation,emphasize

the

levels

of

thyroid

activity

actions

of

thyroid

hormones.

observations, importance in

the

study

of

470

Pharmacological

Research

Communications,

Vol. 17, No. 5. 1985

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Endocri=

=,235,1981.

CASSONE M.C.

and L.MOLINENGO,

D'AMOUR F.E.,F.R.BLOOD ry work

Sci.

and A.D.BELDEN

in mammalian

Chicago-London,

Life

physiology

Jr.

Part

The University

EAYRS J.T.,Brit.Med.Bull.

2,1983,1981. Manual

for

I Exp.25,3rd

of Chicago

Press,

laborato= edn. 1969.

l6,122,1960.

EMLEN W.,D.S.SEGAL

and A.J.MANDEL,Science

FUNDARO' A.,M.C.CASSONE

and L.MOLINENGO,

pharmacol.&Biol.Psychiat. HOFFMAN F.,E.J.HOFFMAN

=,79,1972. Progr.Neuro-Psycho=

2,57,1983. and J.TALESNIK,

Amer.J.Physiol.

148,

689,1947. KREEZER G.L.,in Farris

The rat

in

and J.Q.Griffith

York,p.

laboratory

investigation.

Jr.

Publishing

Hafner

ed E.J. Company,

New

203,1971.

OPPENHEIMER J.H.,H.L.SCHWARTZ

and M.I.SURKS,Endocrinology

2,

897,1974. RASTOGI R.B.

and R.L.SINGHAL,

J.Pharmac.Exptl.Ther.

198,609,

1976. SCHWARTZ H.L.

and J.H.OPPENHEIMER,

and Treatment pp139

of Disease

Pergamon

Press,

in The Thyroid,Physiology

edts.

Hershman

J.M.

and G.A.Bray,

Oxford,1979.

SKINNER B.F.

The Behaviour

Appleton

Century-Crofts,Inc.

of Organism. New York,

VERITY M.A.,W.J.BROWN,M.K.CHEUNG

7th edn,pp.130-131

,

1938.

and G.J.CZER,

J.Neurochem.

2&853,1977. WHYBROWP. and R.FERREL, vior.

ed.A.J.Prange

in The thyroid Jr.,

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axis,

drugs

Raven Press,

New York,

1974. ACKNOWLEDGEMENT. This

research

was supported

by MPI Grant

and beha=

60%,1983