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15. 12.

1972

1461

Specialia

Effects of Repeated Administration of DL-Amphetamine and Methamphetamine on Tolerance to


Hyperactivity
S t u d i e s h a v e s h o w n t h a t t h e s t i m u l a t i n g effect of DLa m p h e t a m i n e on m o t o r a c t i v i t y does n o t d i m i n i s h w i t h
r e p e a t e d t r e a t m e n t of t h e d r u g 1-3. Contrarily, r e p e a t e d
t r e a t m e n t with m e t h a m p h e t a m i n e showed a progressive
r e d u c t i o n in m o t o r h y p e r a c t i v i t y a-5. R e v i e w i n g t h e literat u r e c i t e d above, h o w e v e r , s a l i n e - c o n t r o l s were n o t included in t h e m e t h a m p h e t a m i n e studies. I t seemed, t h e r e fore, d e s i r a b l e t o s u b s t a n t i a t e t h e p r e s e n c e of t o l e r a n c e
to h y p e r a c t i v i t y in a n i m a l s w i t h m e t h a m p h e t a m i n e .
Male S p r a g u e - D a w l e y r a t s w e i g h i n g 230-300 g, or male
Swiss-Albino mice w e i g h i n g 20-25 g were used. T h e y were
fed w i t h W a y n e L a b o r a t o r y B l o x a n d w a t e r ad l i b i t u m .
The r a t s were caged i n d i v i d u a l l y a n d t h e mice were group-

I n t h e e x p e r i m e n t w i t h r a t s p r e t r e a t e d 2 weeks w i t h a
d a i l y dose of 5 m g / k g m e t h a m p h e t a m i n e or saline, inject i o n s of v a r i o u s t e s t doses of m e t h a m p h e t a m i n e , t h e comp o u n d p r o d u c e d d o s e - r e s p o n s e curves s h o w n in t h e Figure.
P e a k a c t i v i t y was o b t a i n e d w i t h 2 m g / k g of m e t h a m p h e t amine. T h e r e was no s i g n i f i c a n t difference in responses to
t h e final t e s t dose of m e t h a m p h e t a m i n e b e t w e e n t h e drugp r e t r e a t e d a n d t h e s a l i n e - p r e t r e a t e d rats. I n t h e o t h e r exp e r i m e n t , groups of 2 mice w e r e p r e t r e a t e d d a i l y w i t h
e i t h e r 2 m g / k g of D L - a m p h e t a m i n e , 0.5 m g / k g of m e t h a m p h e t a m i n e , Or saline a n d m o t o r a c t i v i t y was m e a s u r e d for
4 c o n s e c u t i v e weeks. The results are given in t h e Table.
Our d a t a f r o m t h e p r e s e n t s t u d y s u p p o r t t h e s t a t e m e n t

Effect of chronic injections on motor activity in mouse

Treatments

No.
in group

Weeks after treatment


W0
W1

W2

W3

\V4

Saline

10

1.28 ( 0.53)

1.21 (:~ 0.75)

1.29 (-- 0.73)

1.21 ( 0.73)

1.26 (-t- 0.76)

DL-Amphetamine

10

1.71 (-- 0.84)

1.76 ( 0.79)

1.80 (-- 0.83)

2.08 ( 0.93)

2.10 (-F 1.09)

2.19 (J: 0.53)

2.51 (q- 0.63)

2.54 (~ 0.99)

2.74 ( 1.21)

2.86 ( 1.04)

Methamphetamine

Values represent total motor activities in thousand counts i 1 S.D. between 30 to 60 mill after the injection.

t h a t n L - a m p h e t a m i n e i n j e c t i o n s do n o t p r o d u c e t o l e r a n c e
to h y p e r a c t i v i t y . H o w e v e r , t h e lack of t o l e r a n c e to m o t o r
a c t i v i t y in a n i m a l s t r e a t e d w i t h m e t h a m p h e t a m i n e is n o t
in a g r e e m e n t w i t h t h o s e works r e p o r t e d previously.

Is)
1.00

0.75

Rdsumd. Cette 6rude c o n c e r n e le d 6 v e l o p m e n t d ' u n e


a c c o u t u m a n c e de l ' a c t i v i t 6 m o t r i c e chez les a n i m a u x qui
o n t 6t6 trait6s avec de la m 6 t h a m p h 6 t a m i n e ou a v e c l a
DL-amph6tamine. Nos r6sultats i n d i q u e n t q u ' i l n ' y a p a s
d ' a c c o u t u m a n c e chez les a n i m a u x qui o n t 6t6 trait6s de
n L - a m p h 6 t a m i n e ou de la m 6 t h a m p h 6 t a m i n e .

oE

t,t3

0.50

~o

o.25
(9)
0

Tzu-CHIAU Lu, BENG T. H o a n d W. M. MclSAAC 6


0.5

8rng/kg

Effect of methamphetamine on the motor activity of rats pretreated


2 weeks with a daily dose of 5 mg/kg of methamphetamine ( 9169
and of control (@--@).

Texas Research Institute o/Mental Sciences,


7300 Moursund Avenue, Houston (Texas 77025, USA),
7 April 1972.

ed 2 in each group. The a n i m a l s r e c e i v e d d a i l y b e t w e e n


16.00 a n d 16.30 h a n i.p. i n j e c t i o n of 1.0 m l / k g b o d y w e i g h t
of D L - a m p h e t a m i n e sulfate or m e t h a m p h e t a m i n e h y d r o chloride dissolved in isotonic saline. T h e c o n t r o l g r o u p was
i n j e c t e d w i t h a c o r r e s p o n d i n g v o l u m e of isotonic saline.
I n d i v i d u a l s r a t s or groups of 2 mice were p l a c e d in a p h o toelectric cage, for m e a s u r e m e n t of m o t o r a c t i v i t y . All
a c t i v i t y m e a s u r e m e n t s were m a d e in t h e a f t e r n o o n a n d
b e t w e e n 30 t o 60 rain a f t e r t h e injection. F o r s t a t i s t i c a l
a n a l y s i s of t h e d a t a S t u d e n t s t-test or v a r i a n c e analysis,
a n d a level of p < 0.05 was a d o p t e d to assess t h e signific a n c e of t h e difference of means.

1 j. TORMEY and L. LASAGNA,J. Pharmac. exp. Ther. 128, 201


(1960).
2 C. R. SCHUSTERand J. ZIMMERMAN,J. exp. Analysis Behav. 327
(1961).
~. E. KOSMAN and K. R. UNNA, Clin. Pharmac. Ther. 9, 240
(1968).
a H. UTENA and S. TAKANO, Folia psychiat, neurol, jap., SuppL
6, 38 (1960).
5 E. E. SnlLLITS, Br. J. Pharmae. 25, 248 (1966).
6 This research was supported in part by U. S. Public Health Service
Grant No. MH-12959.