Time-dependent learning deficit caused by hydroxylamine

Likewise. the reliable performance decrement on Extinction Da) 1 rar each group except SOSA presumably reflected the tendency uf nonshock aftereffects to elicit vigorous escape behavior for SOSA. Unfortunately the effects of 50SA were transient. Later extinction data showed a reliable decrement in 50SA's performance similar to that of other groups. This decrement may have reflected the modification of nonshück aftereffects für SOSA by successive extinction trials. RlFERENCES UlOO\1. 1. \1.. & CAPALDI, E. 1. The behavior or rats in relation to complex patterns of partial reinforcement. Journal 01' Comparative & Ph y siologica! Psychology, 196 I. 54, 261-265. [RANCHINA, J. J. Transfer of escape training. Journal of Comparative & Physiologlcal Psychology, 1968, 65,175-178. FRANCHlNA, J. J. Intertria! inlervals and shock schedules in escape training. Journal of Comparativc & Physiological Psychology, 1969.67.510-515. Time-dependent learning deficit caused by hydroxylamine ST ANISLA V REINIS Department üf Physiology, Ghana Medical School, Accra, Ghana'" The effect of O.5-M hydroxylamine injected intracranially on a passive-avoidance task was followed in mice. Hydroxylamine administered 24 h before the acquisition trial or earlier had no effect on performance of animals. Hydroxylamine injected 2 h before the acquisition trial impaired the performance of animals tested 24,48, 72 h, or 1 week later. Hydroxylamine injected 1, 2, or 24 h later interfered with the performance of animals, too. The later hydroxylamine was injected, the later the impairment of performance of animals appeared. The effect of hydroxylamine is probably associated with the "mutagenic" action of the drug on activated DNA. In our previous papers (Reinis, 1970a, b), we described the effect of hydroxylamine on retention of two different learning situations-alimentary conditioning and learned preference to one arm of a water maze. We associate the effect of hydroxylamine on learning with the metabolie disturbances of the affected nerve cells, from which the transcription of changed DNA may be one of the important constituents. Hydroxylamine is bound to several nuc1eotides of activated derepressed DNA and eauses "misreading" of the code. Abnormal proteins are synthetized (Beguin & Kepes, 1963), which may be responsible for the delayed effect of the drug. In the present paper we tried to correlate the interval between acquisition trial and hydroxylamine injection with the time of appearance of the behavioral *Present address: Department of Psychology. York University, 4700 Keele Street, Downsview 463, Ontario, Canada. Psychon. Sei., 1970, Vol. 21 (3) effeet. We tried also to demonstrate the effeet of hydroxylamine on learning in passive-avoidance situations where the performance is not dependent as much on general state and physical fitness of the animal as on alimentary conditioning or swimming in the water maze. MATERIAL AND METHOD The experiments were performed on 840 Swiss albino mice of the strain reared in University of Ghana Medieal Schoo! in Accra. Rat males, weighing 25-30 g and aged at least 2 months, were used for the experiment. The mice were brought 4-5 days befoTe the experiment into an air-conditioned room (23°C) and kept in this room up to the end of the experiment. The apparatus consisted of a covered wooden chamber 28 x 28 x 25 cm. A narrow chamber, 16 x 11 x 28 cm, made from semitransparent acrylic plastic, was attached to the wooden box. The wooden ehamber was provided with a grid floor wired to apower supply that administered a 4.5-mA, 100-Hz footshock to the animal when it entered it through a 7-cm-diam hole conneeting the two chambers. The mice were placed into the sm alle r transparent lighted chamber from which they stepped spontaneously into the bigger dark one. The interval between the placement of the animal into the lighted compartment and its entry through the hole into the darkened chamber (response latency) was measured in this acquisition trial. T h e 0.5 -M hydroxylaminehydrochloride , adjusted by sodium hydrOXide to pH 7.35, was injected intracranially in the dose of 10 mieroliters towards each homisphere. For contral injections, 0.5-M saline was used. The mice were slightly narcotized with ether, and the skin of the head was cut in the middle line. A thin injection needle was advanced through the temporal muscle. This prevented leakage of the fluid from the skull. Groups of animals were injected 2 weeks, 1 week, 72, 48, 24, and 2 h be fore the acquisition trial and 1, 2, 4, and 24 h after the acquisition trial. Each injection group was split into four test-time groups, the first being tested 24 h, second 48 h, third 72 h, and fourth 1 week after the acquisition trial. Each animal was tested only once. Ihere were 12 animals in each test-time group. The test trial was conducted in essentially the same fashion as the acquisition trial. The latency of entering the dark compartment was measured with a stopwatch. A 30o.sec cut-off time was used for the test trial Table 1 Response Latency in First (Acquisition) Trial in Mice Injected by Hydroxylamine Saline Injection Number of Animals No injection before trial 360 2 weeks before 1 week before 72 h before 48 h befote 24 h before 2 h before 24 24 48 48 48 48 Hydroxylamine Time in Seconds NUljIber of Animals Time in Seconds 19.1 sec 21.1 22.7 17.8 15.3 21.6 17.4 24 24 48 48 48 48 18.3 16.7 20.0 23.0 25.2 17.4 179 Table 2 Numbet of Mice That Did Not Enter the Dark Space in the Second (Testing) Session of Passivc·Avoidancc Task --- ----~--- Interval Betwcen the Acquisition an~~csting .:!!ial~,-- ~_ Interval Between Injection and Acquisition Trial 2 weeks before 1 week before 72 h befote 48 h before 24 h before 2 h before 1 h after 2 h after 4 h after 24 h after 24 H 48 H Hydroxyl· amine Saline HydroxylSaline amine 10 11 9 8 8 9 10 7 9 9 0 4 7 9 p< .02 response latency. There were always 12 animals in one group. The number of mice that entered the dark chamber earlier than 300 sec was evaluated statistically by a chi-square test. RESULTS Table 1 demonstrates the average response latency in the first (acquisition) trial. There are no statistically significant differences between the intact mice without any injection and mice injected intracranially by hydroxylamine or saline. In Table 2 the retention of passive avoidance in mic~ affected by hydroxylamine is shown. The injection of hydroxylamine performed from 2 weeks to 24 h before the acquisition trial is ineffective. Hydroxylamine administered 2 h before the acquisition trial has a very high effect on performance of animals in the testing trial; this may be demonstrated as early as 24 h after the training and persists up to the testing session 1 week after training. Hydroxylamine injected 1 h after the acquisition trial affects the performance of the animals within 48 h after injection. The effects of hydroxylamine injected 2 or 4 h after the fir (...truncated)