Psychopharmacologia (Berl.) 16, 49-53 (1969)

The Effect of Strychnine Administration

during Development on Adult Maze Learning in the Rat

BURNEY J. LE BOEUF

Crown College University of California, Santa Cruz, California

HARMAN V. S. PEEKE

Department of Psychiatry, University of California, San Francisco Medical Center

Received April 29, 1968

Final Version: July 11,1969

Summary. Strychnine sulphate administered to rats during post-natal de­velopment affected the rate of maze learning in adulthood. Rats given the drug in a rich environment (drug-rich group) learned a maze at a faster rate than rats treated similarly but raised in laboratory cages (drug-caged group). The performance of rats given no drug was intermediate to that of the drug-rich and drug-caged groups.

Key- Word8: Drugs - Environment - Learning - Neural Stimulant - Strych­nine Sulphate.

Several experiments have demonstrated that single sub convulsive doses of the neural stimulant, strychnine sulphate, facilitate maze learning in the mature rat, whether administered prior to or immediately following maze trials (see McGaugh and Petrinovich, 1965, for a recent

review). The purpose of the present study was to determine whether administration of this drug during post-natal development would affect the rate of maze learning in the adult rat.

Hebb (1958) has shown that altered environment during development can modify behavior in adulthood. In addition, it has been suggested that strychnine and related drugs may affect the animal's perception of his environment during the period when the drug is active (Meier and Huff,

1962). It is likely that drug-induced changes in perception of the environ­ment will interact with and perhaps enhance the behavioral effects of an altered environment. One might expect the drug's effects to be dependent upon the environment in which the animals were maintained during its administration.

Method

Twenty male and 20 female rats of the K strain, descendants of crosses between Tryon's Sl and S3 strains (Tryon, 1940), were obtained from 6 litters and randomly assigned at 21 days of age to four treatment

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groups of 10 animals each: 1. Drug-Rich (DR)-daily strychnine injec­tions in a rich environment; 2. Drug-Caged (DC)-daily strychnine injections in a caged environment; 3. Saline-Rich (SR)-daily saline injections in a rich environment; and 4. Saline-Caged (SC)-daily saline injections in a caged environment.

The rich environment consisted of a cage 4 ft. wide X 4 ft. long X 2 ft. high with wire mesh sides, the interior of which was furnished with various black and white painted objects patterned on those employed by Krech, Rosenzweig and Bennett (1960). The position of the objects was changed daily in an attempt to maximize the complexity of the environment. The subjects in groups DC and SC were raised in wire laboratory cages 7 inches wide X 13 inches long X 6 1/2 inches high, the bottoms of which were covered with sawdust.

The subjects were housed and treated in these environments from day 21 to day 52. During this period, a total of 10 Ss from the DR and SR groups were housed together in the rich environment cage. The limited space in this cage made it necessary to run the experiment in two replica­tions. Since the two replications were not differentially affected, the experiment is reported as one. The subjects in groups DC and SC were paired and housed in laboratory cages. During the treatment phase, each subject in groups DR and DC received a daily intraperitoneal injection of 0.5% solution of strychnine sulphate in water suspension, 2.0 cc/kg of body weight or 1.0 mg/kg of body weight. One mg/kg is a dosage previously found to facilitate learning in the rat (e.g., McGaugh and Petrinovich, 1959; Petrinovich et al., 1965). Groups SR and SO were similarly injected with physiological saline, the amount adjusted to body weight as with the strychnine.

On day 52, treatment was terminated and all subjects were paired on a like-sex basis and placed in laboratory cages identical to those previously described until testing began. Individuals from all groups were paired on a random basis.

Prior to maze trials, subjects were put on a 23 1/2 hour food depriva­tion schedule which was maintained throughout the experiment. Once the animals were down to 85 °/0 of their original weight, they were pre­trained in a 24-inch runway leading from a start box to a goal box containing wet mash. Daily trials in a 4 unit, 8 cuI Lashley III Alley­Maze to a wet mash reward began when the subjects were 107 days old. Errors per trial and time per trial were recorded. The criterion of learning was four out of five errorless runs. An error was scored each time half or more of the animal's body extended over the mark indicating a cuI. The number of different culs entered at least once per trial (initial errors) are reported.

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Results

Adult maze performance was affected by administration of strychnine sulphate during development. The direction of the effect, i.e., enhance­ment or illlpairment, varied as a function of the treatment environment. Two measures were analyzed: trials to criterion and initial errors to criterion.

An analysis of variance of the mean trials to criterion revealed a reliable interaction between the drug condition and the rearing environ­

ment (dt = 1.36; F = 4.99; P < .05). A similar significant interaction was found for mean initial errors to criterion (dt = 1.36; F = 4.39; P < .05). The first trial was excluded in the computation of this statistic. The data are presented graphically in terms of group means in Fig_1.

As can be seen in Fig.1 group DR required fewer trials to reach criterion (X = 7.2) and made fewer initial errors in reaching criterion (X = 3.4) than other groups. The DC group was the last to reach criterion (X = 16.3 trials) and made more initial errors in doing so (X = 21.8) . Groups SR and SC obtained similar scores on both of these measures intermediate to the performance of the drug groups.

t·tests between groups corroborated the impression given by the figure. With both measures there is a significant difference between the

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DR and DC groups (trials to criterion t = 3.47, dt = 18, P < .01 and initial errors to criterion t = 2.88, dt = 18, P < .01). With neither

measure was there a difference between DR and SR groups, although the

means are in the predicted direction. In the case of the C condition

administration of strychnine had a deleterious effect on later maze learning. Indeed, the difference between DC and SC is statistically reliable in the case of trials to criterion (t = 2.10, dt = 18, P < .05) though not

quite with the measure of initial errors (t = 1.86, dt = 18, .10> P> .05).

The four groups did not differ in starting or terminal weights or In the speed of running the maze during trials without error.

Discussion

The principal finding of this study IS that strychnine sulphate administered daily for a period during postnatal development interacted with the environment in which the animals were raised to produce effects on their maze learning ability long after administration of the drug had

been terminated. The most striking aspect of this effect is that the major influence of the drug appears to be on the behavior of rats reared in the restrictive environment of the colony cage. Rats which had received

strychnine during maturation in that environment exhibited consistently lower learning capacity in adulthood than a group from the same

environment injected with normal saline. One interpretation of this result is that strychnine, which has been

shown to facilitate learning in a wide range of tasks, enhanced the learn­ing of a "set" to attend to and discriminate among the stimuli within

the narrow perceptual field available in the relatively constant and perceptually impoverished environment of the laboratory colony cage. Such a narrow discriminative and attentional "set" may well have

carried with it into the maze testing situation, with its relatively numer­ous and varied intra- and extra-maze cues, an inability to attend to and make use of those cues, and a proclivity for attending to cues not highly correlated with efficient learning of the maze.

However the results reported here are interpreted, the phenomenon

is more general than only the results of this study would indicate. Shandro and Schaeffer (1969) have recently reported very similar results

to those reported here, including the impoverished environment plus drug decrement in maze ability, using a different strain of the same species, a different maze, a different strychnine dosage and a shorter drug treatment period during development.

Neither the present study nor the report of Shandro and Schaeffer provides evidence that the effects observed are restricted only to a period in development. It is a distinct possibility that strychnine administration

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altered in a manner simila - -

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on adult behavior. This clo-:- =-­-

that environmental exper'. =-­neural stimulant to procluc­Whether or not the effect ­ >­

and, if so, what may be tt.o questions for further resear :.':,

Hebb,D. 0.: A textbook of ps�-::_ Krech,D., lVI. R. Rosenzweig.

plexity and training on braiL (1960).

lVIcGaugh, J. L., and I�. Petrino,: _

learning. Amer. J. Psycho!. 7:!. - - Effects of drugs on learni:.

(1965). lVIeier, G. W., and F. W. Huff:

administration during infanc:' c. 469-471 (1962).

Petrinovich,L. F., D. Bradford. 6.r:

in rats. Psychonom. Sci. 2, HI1- -':

Rosenzweig, lVI. R., E. I�. Bennett. :;:. complexity and training allioe: 438-439 (1964).

Shandro,N. E., and B. Schaeffer: :::. learning. Paper presented a " '-­

Vancouver, B. C., June 1969. Tryon, R. C.: Genetic differences ir:

Stud. Educ. 39,111-119 (19J(1 .

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53

and environment might very well interact during adulthood to produce

results similar to those reported here. Indeed, Rosenzweig, Bennett and Krech (1964) found that the cerebral brain weights of rats could be

altered in a manner similar to their findings with rats reared in complex environments, by giving rats the same kind of experience in adulthood. The same kind of interpretation may apply to drug-environment effects on adult behavior. This does not, however, detract from the basic finding that environmental experience during development interacts with a neural stimulant to produce differences in adult maze learning ability. Whether or not the effect is restricted to a period during development and, if so, what may be the parameters of the "sensitive period", are questions for further research.

References

Hebb, D. 0.: A textbook of psychology. Philadelphia: Saunders 1958. Krech, D., M. R. Rosenzweig, and E. L. Bennett: Effects of environmental com·

plexity and training on brain chemistry. J. compo physiol. Psychol. 53, 509-519 (1960).

McGaugh, J. L., and L. Petrinovich: The effect of strychnine sulphate on maze· learning. Amer. J. Psychol. 72, 99-102 (1959).

- - Effects of drugs on learning and memory. Int. Rev. Neurobiol. 8, 139-196 (1965).

Meier, G. W., and F. ,"V. Huff: Altered adult behavior following chronic drug administration during infancy and prepuberty. J. compo physiol. Psychol. 55, 469-471 (1962).

Petrinovich, L. F., D. Bradford, and J. I,. McGaugh: Drug facilitation of memory in rats. Psychonom. Sci. 2, 191-192 (1965).

Rosenzweig, M. R., E. L. Bennett, and D. Krech: Cerebral effects of environmental complexity and training among adult rats. J. compo physiol. Psychol. 57, 438-439 (1964).

Shandro, N. E., and B. Schaeffer: Environment and strychnine: Effects on maze learning. Paper presented at Western Psychological Association meetings. Vancouver, B. C., June 1969.

Tryon, R. C.: Genetic differences in maze.learning ability in rats. Yearb. Nat. Soc. Stud. Educ. 39,111-119 (1940) .

Burney J. Le Boeuf Assistant Professor of Psychology Crown College, University of California Santa Cruz, Calif. 95060, U.S.A .

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