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The effects of chronic exposure to low levels of lead via maternal milk during the neonatal period in the rat were evaluated by means of several activity measures, spontaneous alternation in the Y-maze, and weight data. Animals reared at the highest concentrations of lead showed retarded body growth. Lead-treated rats were found to be more active in the Y-maze and in the tilt-box, but not in the running wheel. Lead-treated rats showed lowered spontaneous alternation and increased squealing; results were dependent upon the concentration of lead on which the animals were reared. Activity and alternation data provide suggestive evidence of lead-induced damage of the hippocampus, a structure which undergoes much of its development during the stage in which the lead was administered. Behavioral parallels found between lead poisoning and childhood hyperactivity were discussed with respect to the utility of chronic low level lead administration as an animal model of minimal brain dysfunction hyperactivity.

Fifty-four male hooded rats were observed for two sessions, 8 min. each for continuous spontaneous alternation in a Y-maze. Subjects were found to alternate on 71% of all choices. Responsivity decreased during each session and a decided preference was shown for the initial placement arm regardless of its spatial position. Though arms per se did not affect alternation, the amount of time spent in previous arms differentially affected alternation depending on whether the subject was displaying alternation or non-alternation behavior during the preceding trials. Results are discussed in terms of their implications for stimulus satiation models of spontaneous alternation behavior.

A learned aversion to a walnut solution paired with lithium carbonate was examined in rats with lesions of the dorsal hippocampus. While preconditioning CS exposure retarded conditioning in controls, this same manipulation did not affect suppression to the CS in animals with lesions and, in fact, resulted in greater stimulus control in these subjects. These results support the view that the hippocampus is involved in the modulation of attention.

SummaryThe addition of nicotinamide adenylate compounds was found to maintain, to a significant extent, the glycolytic capacity of fresh human erythrocytes incubated in vitro for 20 hours. The compounds appeared to act also to restore the metabolism of aged cells. Although it is not believed that nucleotides readily enter the intracellular compartment, evidence is presented that erythrocytes can slowly assimilate adenine nucleoside phosphates. The possible role of erythrocyte phosphomonoesterase is discussed.

Rats were trained in a straight runway on a non-spatial single alternation (NSSA) which involved presentation of reward (R) and nonreward (N) in a fixed repeating sequence (i.e. R-N-R-N ...). Patterned running results since rats learned to run fast on R trials and slow on N trials. This task can be regarded as an animal analog of the goal directed serial alternation task employed with humans. After patterned running was well established the effects of graded doses of δ9-THC, LSD and scopolamine were delineated. Although all drugs modified alternation performance, each agent produced distinctly specific effects on the different components of NSSA. δ9-THC disrupted alternation by decreasing running speed on R trials and increasing running speed on N trials. Lower doses of LSD increased running speed on N trials while leaving R trial speeds unchanged. At the highest dose, LSD decreased running speed on R trials while leaving N trial speeds only slightly elevated from baseline. Scopolamine disrupted alternation solely by decreasing speed on R trials. The results were discussed with reference to the effects of these drugs on internal inhibition, registration and recall of internal cues and timing behavior.

Rats were exposed to lead via the maternal milk. At 90 days of age, lead-exposed pairs and control pairs were tested for aggression induced by 5.0 mg/kg apomorphine. The large increase in aggression in response to apomorphine seen in controls was markedly attenuated in lead-treated subjects. In contrast, apomorphine-induced stereotypy was not affected. These results provide a further demonstration of persistent behavioral abnormalities resulting from early exposure to lead at levels which do not affect weight gain or mortality.

The effects of d-amphetamine on several measures of activity and spontaneous alternation were evaluated in rats chronically exposed to a low level of lead acetate via maternal milk during the neonatal period. Alterations in the amphetamine responses of lead-treated rats were observed with some measures of activity and exploration but not with others. 'Paradoxical' responses were observed with postural rearing and spontaneous alternation. No drug response was seen in lead-treated animals with respect to center field activity in contrast to a large increase seen in controls. Normally, amphetamine reduces grooming behavior, but since this reduction was greater in lead-reared than in control rats, the data suggest that for this measure the lead-reared rat may posses an increased sensitivity to amphetamines. These results were discussed in terms of the behavioral parallels found between lead poisoning and childhood hyperactivity, and the potential of this model as an animal analog of minimal brain dysfunction hyperactivity.

A battery of tests clinically employed for the estimation of auditory and visual recent memory dysfunction was administered to eight subjects having circumscribed damage to the temporal lobe. It was hypothesized that the performance of subjects with temporal lobe lesions would qualitatively resemble that of subjects intoxicated with marijuana. Where comparisons could be made, the performance of these "temporal lobe" patients paralleled the performance of subjects acutely intoxicated with known doses of delta 9-THC. Results are discussed in terms of cannabinoid actions on hippocampal functioning and, in general, support the hypothesis that the action of marijuana in the brain may focus in the hippocampal region and produce behavioral changes similar to that resulting from traumatic injury or removal of the region.

The effects of δ 9-THC, LSD-25 and scopolamine on continuous, spontaneous alternation of the hooded rat in the Y-maze were determined. LSD and scopolamine decreased the number of arm entries (responsivity) while concomitantly reducing percent alternation. THC however, reduced responsivity and percent alternation more at the lower dose (1 mg/kg) when compared to control than at the higher dose (3 mg/kg). Only scopolamine induced a significant increase in stimulus perseveration. The results are discussed in relation to the advantages afforded by the continuous spontaneous alternation procedure.

Summasy.--4 groups of rats were given injections of scopolamine, methylscopolamine, eserine or saline immediately following the completion of an acquisition trial on a brightness discrimination in a T-maze. Results indicated that eserine and scopolamine groups displayed little or no reduction in errors over 50 acquisition trials, while Ss treated with methylscopolamine or saline showed a marked reduction in errors over the last 15 trials. While the data can be interpreted in terms of a consolidation model of memory, a progressive increase in failures to eat on rewarded trials by groups receiving the centrally active drugs, indicates that side effects of these drugs probably played a role in learning impairments. A number of investigations have indicated that post-trial injections of anticholinesterase drugs can facilitate learning, presumably by accelerating cholinergic processes involved in memory consolidation. Scratton and Petrinovich (1963) have found that the learning of a Lashley I11 maze was facilitated in maze bright and dull rats by post-trial injections of eserine in doses between .25 mg/kg and .75 mg/kg. Doy and Johnston (1966) found that post-trial injections of .5 mg/kg eserine increased simple avoidance responding and improved discriminative avoidance behavior. While some evidence exlsrs thac post-trial injections of anticholinesterases facilitate learning, evidence 1s sparse as to whether post-trial injections of anticholinergics have retroactive inhibitory effects on learning and retention. Anticholinergics attenuate acerylcholine activity at the cholinergic synapse. Bohdanecky and Jarvik ( 1967) have found that post-trial injections of scopolamine had no effect on retention of a one-trial passive-avoidance task. Squire (1969), however, reported that scopolamine (1 mg/kg) given after the first trial of a spontaneous alternation task disrupted alternation performance, while eserine (.4 mg/kg) facilitated it. Recently, Berger (1969) reported thac both scopolamine and methylscopolamine, each at doses of 1 mg/kg, given immediately after ran made 100 licks at a drinking tube, increased drinking latencies upon retesting 6 days later. Furthermore, increasing the trial-injection interval produced a retrograde amnesic effect

Using the open-field activity of the hooded rat as a model of overall activity, the dose-response and time-action effects of doses of Δ9-THC which did not adversely affect spontaneous activity or behavior on appetitively motivated tasks were studied. Subjects received two exposures to an open field one week apart. Prior to the first exposure subjects were treated with small doses of Tween 80-water. At 30 min or 3 h prior to the second exposure subjects were treated with Tween or Δ9-THC in doses which ranged from 0.5–5 mg/kg. Results indicated that Δ9-THC affected various indices of open-field activity such as grooming, sniffing and ambulation differently depending on the time after injection. Rearing and defecation were affected similarly by THC independent of post-injection intervals.

A simple and highly sensitive method of automating the acquisition of activity wheel data on animals in isolation is described. As well as being inexpensive and quickly constructed the modification is entirely maintenance free.

A number of studies have assessed the effect of REM sleep deprivation in animals on the acquisition and retention of various learning tasks. Fishbein (1969, 1970) has found deficits in retention on a one-trial passive avoidance task in mice when REM sleep deprivation either preceded or followed acquisition. If it preceded acquisition, retention deficits were found 24 hr. later bur not from 5 min. to 1 hr. later. If, however, REM sleep deprivation was inrerpolated between training and retest, impairment in retention occurred only if Ss were tested while REM deprived, but not if Ss were allowed sufficienr time to recover. The purpose of the present study was to assess the effect of REM sleep deprivation given before or after the acquisition of a one-trial passive avoidance cask on retention after a brief or extended interval of time. In Exp. I, 1 8 male albino rats approximately 300 days old received a 0.4-ma. shock of 2 sec. duration 5 sec. after passing from a lighted to a darkened comparunent of a rwocomparunent shuttle box. Ten Ss were then subjected to REM sleep deprivation via the inverted flower pot technique (Dement, 1965). Inverted flower pots having a 7 cm. base were used. An animal is placed o n top of rhe pot which is immersed in water (room temperature). A loss of muscle tonus which is concommitant with a loss of REM sleep results in S coming into contact with the water causing it to awaken. Eight Ss served as conrrols and were placed on pots 14.5 cm. in diameter. Such pots allow a certain amount of REM sleep to occur. Food was always available and within easy reach from small hanging wire containers. A record of S's weight was kept each day. As a further control, the 8 control Ss were yoked to 8 of the deprived Ss and were pushed into the water each time a deprived partner fell in. T h ~ s added control proved to be rather unnecessary since most control Ss failed to take advantage ol' the greater surface area of the larger pot while sleeping, and hence fell into the n2ntcr almost as many times as deprived Ss. After 4 8 hr. on the pots, each group was dirrded ~n half and tested for retention 30 min. or 24 hr. after being returned to their home cage. O n the retention trial, all Ss were allowed a maximum of 180 sec. to enter the dark comparunent. Results indicated that only one S in the deprived group ar the 30-min. interval entered the dark compartment within the 3-min. period. N o S in any other condition did so. N o significant weight loss occurred in either group. In Exp. 11, deprived Ss were treated exactly as those in Exp. I, except that REM sleep deprivation was initiated 72 hr. before acquisition training. The control group was housed on sawdust placed on the bottoms of the dry water tanks for the 72 hr. 10 rats served in the experimental group and 6 as controls. All Ss were 100 to 120 days of age. Groups were again divided in half and tested for retention 30 min. o r 24 hr. later. N o S in any condition attempted to enter the dark compartment during the 3-min. interval. One difference between the first experiment and this one was the significant weight loss of deprived Ss of approximately 50 grn. per animal over the 3-day deprivation period. This may be due in part to the use of younger Ss and the extra day of REM sleep deprivation. Results o f these cwo studies indicate that at least in the context of our experimental conditions, REM sleep deprivation either before or after the acquisition of a one-trial passive avoidance task, had no effect on retention in the REM deprived state or after recovery.

NUMEROUS studies in both humans1–3 and animals4 indicate that marihuana and its chief psychoactive constituent, Δ9-tetrahydrocannabinol (Δ9-THC), may have disruptive effects on short term memory. It has been suggested, however, that the memory-disrupting qualities of marihuana in humans may actually be incidental to its effect on normal attentional processes5. Furthermore, interpretation of animal investigations in terms of drug-induced memory disruption may be difficult as Δ9-THC may alter appetitive motivation6. So it is unclear whether performance deficits are a consequence of impaired memory, attention, or motivation.

Two recent articles1,2 report that marijuana interferes with the recall of narrative material learned in either a drug or no drug state and recalled in the drug state, but the evaluation of the results is hampered by (1) the lack of specification of the Δ9-THC content of the marijuana cigarettes and (2) an absence of placebo controls. We have set out to test the effects of marijuana on narrative recall and Stroop colour-word performance and to remedy these defects of experimental design. The Stroop test was selected because performance has been shown to be impaired by depressants Such as amobarbital3 and because marijuana has barbiturate-like effects4.