Atropine effects on delayed discrimination performance of rats.

The effects of atropine sulfate (ATS) and atropine methyl nitrate (ATM) on the conditional discrimination behavior of rats were investigated in eight-hour experimental sessions. Responding of rats was reinforced on either a lighted or a darkened lever depending on whether lights over both levers had been on during the preceding sample portion of the trial. Zero-delay and four-second-delay trials were randomly interspersed. Quality of performance was analyzed using the A' sensitivity measure of signal detection theory. Both drugs reduced both sensitivity and the percentage of trials on which responding occurred (percent response) below saline treatment levels. The two drugs did not reliably differ from each other in their effects on sensitivity during the zero-delay condition, but reliable differences between the two drugs emerged during the four-second-delay condition at doses above 0.8 mg/kg. Percent response recovered more rapidly for animals treated with ATS than responding occurred (percent response) below saline treatment levels. The two drugs did not reliably differ from each other in their effects on sensitivity during the zero-delay condition, but reliable differences between the two drugs emerged during the four-second-delay condition at doses above 0.8 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Rat maze performance after infusion of cross-linked hemoglobin solution.

Neurotoxicity and behavioral performance degradation have previously been observed in rats after exchange transfusions with unmodified stroma-free hemoglobin solutions. We evaluated a diaspirin cross-linked stroma-free hemoglobin solution (HbXL) for evidence of neurotoxicity. Rats that were trained to complete a water alley maze received a clinically-relevant dose (20 ml/kg) of the 14% HbXL solution on top of their normal blood volume. After post-treatment memory testing in the water maze, the same rats were challenged to learn an elevated radial-arm maze. The HbXL and control groups showed no water maze performance degradation after treatment, and all groups demonstrated learning of the radial-arm maze as shown by decreased errors and times to completion. The brains, heart, and livers presented normal histology thirty days after infusion, but six of fifteen animals showed marked renal tubular regeneration. The normal memory and learning performance and brain histology after infusion with HbXL suggests that this hemoglobin solution is not neurotoxic to unhemorrhaged rats.

Chronic stress increases the binding of the A1 adenosine receptor agonist, [3H]cyclohexyladenosine, to rat hypothalamus.

We previously reported an increase in the binding of [3H]cyclohexyladenosine ([3H]CHA) to brain membranes from the hypothalamus of rats sacrificed following three days of chronic stress in an around-the-clock intermittent footshock avoidance/escape paradigm ("sustained performance" stress). Here we report stress-induced increases in [3H]CHA binding to hypothalamic membranes from rats stressed for 14 days in that escape/avoidance paradigm, in rats exposed to repeated restraint (3 hr/day for 10 days) and in rats exposed to four days of "activity-stress." Data from saturation binding experiments indicate that this up-regulation was due to an increase in the apparent number of [3H]CHA binding sites without change in affinity for [3H]CHA. Neither restraint for one three-hr period nor one 15-min exposure to intermittent footshock resulted in significant changes in [3H]CHA binding to hypothalamic membranes. Our present data demonstrate small but consistent increases in the number of [3H]CHA binding sites in hypothalamic membranes from rats stressed in several different chronic stress models but no change by acute stress.

Long-term sequelae of soman exposure: hormonal rhythms two weeks postexposure to a single dose.

Two weeks following a single exposure to either soman (100 micrograms/kg, sc) or saline, rats were sacrificed at 2-hr intervals over a 26-hr period. Trunk blood was collected and plasma was stored until assayed for corticosterone, prolactin, growth hormone, adrenocorticotropin, beta-endorphin, and beta-lipotropin. Rats surviving for 2 weeks following soman appeared well groomed and were gaining weight at a rate similar to saline-treated rats at the time of termination. Thus, they appeared to have recovered from the initial physiological effects of soman exposure. However, substantial differences in plasma levels of most hormones were seen in comparing soman- vs saline-treated rats. Levels of prolactin were suppressed at all time points in soman-treated rats. Growth hormone secretion was also suppressed and the normal episodic peaks of growth hormone were missing in soman-treated rats. Both soman- and saline-treated rats displayed circadian rhythms in levels of plasma corticosterone, but the usual late afternoon rise in plasma corticosterone levels was shifted to earlier time points in the soman-treated rats. Levels of beta-endorphin and beta-LPH were slightly but significantly suppressed in soman-treated rats at almost all time points. Levels of adrenocorticotropin were similar in control and soman-treated rats. The results of this experiment demonstrate that a single exposure to soman may have long-lasting effects on neuroendocrine function.

Effects of stress on [3H]cyclohexyladenosine binding to rat brain membranes.

The investigation of stress-induced changes in neuronal functioning is important to our understanding of mental disorders, stress-induced psychological impairment, and the emotional reactions of fear and anxiety. Data from previous animal studies have demonstrated various pituitary-adrenal responses to stress and also changes in brain neurotransmitters. We are investigating whether stress-induced neuroendocrine and brain monoamine changes are accompanied by concomitant changes in brain neurotransmitter and/or neuromodulator receptors. We have developed a behavioral paradigm of chronic stress which incorporates sustained stress, continuous performance, and disruption of sleep. Animals which are habituated to press a lever to receive food are trained in an active shock escape task. A matched set of animals housed in identical operant chambers but not exposed to footshock are used as comparative controls. [3H]Cyclohexyladenosine ([3H]CHA) (5-7 nM) binding to A1 adenosine receptors in hypothalamic membrane preparations from rats stressed for three days was fifteen percent higher than in matched controls. However, no differences in [3H]CHA binding were found in tissue preparations from frontal cortex, hippocampus, or striatum, when comparing stressed and matched control rats. Plasma corticosterone levels were higher in stressed rats than in matched controls.

Effects of chronic stress on plasma corticosterone, ACTH and prolactin.

Rats were placed in a stressful environment for 24 hr per day and levels of plasma hormones were measured after varying numbers of days in the environment. Rats were habituated to operant chambers placed in sound-attenuated enclosures. Food pellets were available by lever press on a FR1 schedule. After 3 days of habituation, rats in the "stressed" group were trained to pull a ceiling chain to avoid or escape shock. Following training, stress trials, consisting of a consecutive sequence of 5 sec each of a warning light, warning tone and 0.16, 0.32, 0.65, 1.3 and 2.6 mA of footshock, occurred approximately once per 5 min around-the-clock. For the first day, the sequence was terminated when the ceiling chain was pulled. On subsequent days, 90% of all shock presentations could be avoided or escaped by chain pull; the remaining 10% of trials were inescapable and the entire sequence was presented. Control rats lived in identical chambers without presentation of shock. Rats were sacrificed after 1, 2, 3, 4, 7 or 14 days in this environment and levels of plasma corticosterone, ACTH and prolactin were determined. Levels of plasma corticosterone were elevated during the first 7 days in the stressful environment, but returned to control values by day 14. Levels of plasma ACTH and prolactin were similar in stressed and control rats at all time points measured. These data suggest that stress-induced changes in glucocorticoids but not in ACTH or prolactin might mediate some of the physiological changes that occur as the result of chronic stress.

The effects of diisopropyl phosphorofluoridate (DFP) on inter-response time and circadian patterns of lever-pressing in rats.

Rats were injected with saline, 1.0 mg/kg or 2.6 mg/kg of diisopropyl phosphorofluoridate (DFP). Three days later the animals were placed in cages in which they could press a lever to obtain their entire daily ration of food. The time of day at which responses occurred and the time between successive responses were recorded over a six day period to determine the circadian pattern of lever-pressing and the distribution of inter-response times (IRTs). The saline injected rats exhibited a normal nocturnal pattern of feeding, while both DFP treated groups exhibited a significantly greater tendency to eat during the day. Analysis of the IRT distributions of the three groups showed a different pattern of results. The saline and 1.0 mg/kg DFP groups produced nearly identical IRT distributions, while the 2.6 mg/kg group produced an IRT distribution which was marked by significant increases in the interquartile range and median IRT. Since the 1.0 mg/kg dose of DFP produced a circadian disruption but did not affect the IRT distribution, it appears that the disruption of circadian activity by DFP which was reported by Raslear and Kaufman cannot be solely explained by simple changes in the motor response.

Memory for faces: testing method, encoding strategy, and confidence.

Signal detection theory predicts a square root 2 recognition memory performance advantage for the two-alternative forced choice (2AFC) procedure over the yes-no (YN) procedure. In auditory psychophysics this advantage has been related to greater demands on memory in the YN task. The present experiment tested this prediction by assessing face-recognition accuracy and confidence in 72 college student subjects. Testing method (2AFC or YN) and encoding instructions (standard, overall gestalt, or distinctive feature scan) were varied, the latter in an effort to vary trace strength to see whether stronger traces would yield a lesser 2AFC advantage. A 1-week retention test revealed an overall 2AFC advantage of 1.61 and superiority of gestalt and feature-scan instructions over standard ones. While confidence and accuracy were related both within and across subjects, 2AFC subjects were significantly more confident than YN ones. Intriguingly, more efficient encodings resulted in a greater, rather than a lesser 2AFC advantage.