Diurnal patterns in brain biogenic amines of rats exposed to 60-Hz electric fields.

Levels of brain neurotransmitters and their metabolites, as well as concentrations of enzymes associated with their synthesis and metabolism, fluctuate during the day in patterns defined as circadian. The present study examined these rhythms in albino rats exposed to 60-Hz electric fields. Thirty-six animals were exposed to a 39 kV/m field for 4 weeks, 20 h/day, in a parallel-plate electrode system. A group of 36 sham animals was similarly handled and housed in a nonenergized exposure system. On the sampling day, animals were sacrificed at 4-h intervals throughout the 24-h day. Brains were removed, dissected, and kept frozen until chemically analyzed. The levels of biogenic amines and their acidic metabolites in the striatum, hypothalamus, and hippocampus were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) methods. Repeated exposure to 60-Hz electric fields produced significant alterations in the diurnal rhythms of several biogenic amines: dihydroxyphenylacetic acid (DOPAC, the primary metabolite of dopamine in the rat) in the striatum, and norepinephrine, dopamine, and 5-hydroxyindoleacetic acid (5-HIAA; serotonin metabolite) in the hypothalamus. Levels of serotonin in the striatum and hypothalamus showed clear circadian patterns that was not affected by the field. No diurnal or field-related changes were observed in the hippocampal amines.

Learning and memory in young and aged Fischer 344 rats.

Changes in learning and memory processes that occur with senescence were investigated in male and female Fischer 344 rats, 3-26 mth of age. Age-related impairments were seen in retention of inhibitory avoidance learning, acquisition of a Y-maze discrimination task, and in a swim escape task with short intertrial training intervals. In contrast, old animals performed better than the young rats in an active avoidance task. No age differences were observed in either open field activity or in flinch or jump thresholds to footshock. These results indicate that impairments in learning and memory processes of aged rats are task-specific, and that memory deficits in old rats are best seen following one-time-only events or with weak training. The behavioral baselines described will help in the design of further research to correlate memory and neurobiological changes observed during the aging process in the rat.

Post-training amygdaloid lesions impair retention of an inhibitory avoidance response.

The study examined the effect of pre- and post-training bilateral amygdaloid lesions on retention of a one-trial inhibitory avoidance response. Groups of rats, including unimplanted controls and implanted controls, were trained and tested for retention at 4, 7 or 12 days following training. The lesions were made at one of several intervals before or after training: 2 days before, immediately after, or 2, 5 or 10 days after. At all retention intervals the retention of implanted controls was poorer than that of unimplanted controls and, in comparison with both control groups, the retention of animals lesioned before training was impaired. Retention was also impaired by the post-training lesions. The degree of impairment varied with the interval between the training and the lesion: lesions made within 2 days following training impaired retention, while lesions made 10 days following training had no impairing effect. These findings suggest that post-training lesions of the amygdala affect retention by impairing time-dependent processes involved in memory storage. With a sufficiently long training-lesion interval (10 days) an intact amygdala is not essential for retention.

Age-related changes in the catecholamine content of peripheral organs in male and female F344 rats.

Norepinephrine levels of old and young F344 rats of both sexes were compared in several organs that receive sympathetic innervation. In addition, both norepinephrine and epinephrine concentrations in the adrenal medulla of young and old rats were determined. A rationale was developed for making age-related comparisons of the catecholamine content in peripheral organs which accounted for age-related changes in organ weight and body weight. It was found that norepinephrine concentrations were decreased for old male rats in heart auricles. In contrast, in old female rats there were no age-related changes in the catecholamine content of any peripheral organ.

Alterations in dihydromorphine binding in cerebral hemispheres of aged male rats.

Equilibrium binding of [3H]dihydromorphine was assayed in brain regions of young and aged male F344 rats. Young rats had significantly higher receptor densities than old rats in the frontal poles, anterior cortex, and striatum. In the frontal poles, the decline in receptor concentration with age was accompanied by a significant increase in the apparent affinity of dihydromorphine for receptors, which may be compensatory for the decrease in Bmax. This pattern of receptor alterations is different than that previously observed in aged female rats. Therefore, processes which underlie synaptic alterations with age may be different in males and females.

Attenuation of amphetamine-induced enhancement of learning by adrenal demedullation.

These experiments investigated the effect of immediate posttrial administration of peripherally acting DL-4-hydroxyamphetamine on retention of a one-trial inhibitory avoidance response in intact, adrenal medullectomized, sympathectomized, and medullectomized and sympathectomized rats. In intact rats, 0.82 mg/kg of DL-4-OH-amphetamine enhanced retention performance. In rats sympathectomized by peripheral 6-hydroxydopamine, 24 h prior to training, a lower dose of 4-OH-amphetamine (0.21 mg/kg) was most effective in enhancing retention. Adrenal demedullation abolished the memory enhancing effects of DL-4-OH-amphetamine and also D-amphetamine. These findings suggest that the memory enhancing effects of DL-4-OH-amphetamine and D-amphetamine involve adrenal medullary catecholamines.

Enkephalin and fear-motivated behavior.

Leu[Enkephalin (400.0 micrograms/kg) and the enkephalin analog [DAla,DLeu]enkephalin (0.4, 4.0, and 40.0 micrograms/kg) were intraperitoneally administered to rats 5 min before they were trained on aversively motivated tasks. The peptides impaired acquisition of a one-way active avoidance response, facilitated acquisition of an inhibitory avoidance response, and had no effect on acquisition of a swim-escape response. The data indicate that the enkephalin effects are not mediated through actions on locomotor activity, pain perception or reactivity, or light sensitivity. Rather, we suggest that [Leu]enkephalin and its analog strengthen the tendency of rats to suppress behavior in the presence of cues previously associated with aversive stimulation. This effect may be due to an enkephalin-induced increase in fear or arousal. The enkephalin effect on behavior was obtained at low doses and was observed within a few minutes after administration. These findings are consistent with the interpretation that enkephalin effects may be initiated at a peripheral site.

Central and peripheral actions of amphetamine on memory storage.

These experiments investigated the effects of central (intracerebroventricular) and peripheral (i.p.) posttraining administration of D-amphetamine on rat's retention of a one-trial inhibitory avoidance response. While retention was enhanced by i.p. administration (1.0 mg/kg) the central administration (dose range 50-500 microgram) did not affect retention. In rats given peripheral 6-OHDA 24 h prior to training a lower dose (i.p.) of amphetamine (0.25 mg/kg) was most effective in enhancing retention. These findings suggest that the mrmory enhancing effects of D-amphetamine are mediated at least in part through peripheral systems.

Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice.

These experiments were performed to examine the effects of graded doses of diazepam, flurazepam, or lorazepam given to Swiss-Webster mice either 30 min prior to training or immediately after training in a one-trial inhibitory (passive) avoidance task. A 350 MUA footshock was administered following entry into a darkened compartment and retention was tested three days later. Doses of 10.0 mg/kg diazepam and 20.0 mg/kg lorazepam given before training significantly impaired acquisition, while 1.0 mg/kg flurazepam, given immediately after training, produced retrograde amnesia. These results indicate that benzodiazepines affect memory processes and that various drugs of the benzodiazepine family differentially affect acquisition and memory consolidation.

Acquisition deficits induced by sodium nitrite in rats and mice.

Graded doses of sodium nitrite were administered shortly before or immediately after a single training trial in an inhibitory avoidance task. A retention test was given at 24 h (rats) or 72 h (mice) after training. The results indicate that sodium nitrite impairs acquisition of an inhibitory avoidance response in rats and mice. Retention was impaired with doses lower than those required for producing hypoxic effects, as measured by the EEG, methemoglobin levels in the blood, blood pressure, and heart rate. Since hypoxia was not involved, it is likely that the effects were mediated by some direct action of sodium nitrite on the CNS.

Experimental tests of hypotheses about neurochemical mechanisms underlying behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate.

Neurochemical and psychopharmacological studies of rats were designed to examine four hypotheses which have been proposed to account for the development of behavioral tolerance to the anticholinesterase, diisopropyl fluorophosphate (DFP). The fact that the activity of the enzymes, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase, did not change concomitantly with behavioral measures during chronic treatment with DFP suggests that nonspecific metabolic changes are unlikely mechanisms of behavioral tolerance. Similarly, a lack of change in choline acetylase activity coupled with constantly high acetylcholine levels (140%) and low cholinesterase activity (28.5%) tends to eliminate end-product inhibition of acetylcholine synthesis as a primary mechanism of tolerance to DFP. Alpha-Methyl-p-tyrosine in doses to 150 mg/kg affected the behaviors of control and DFP-treated rats to a comparable degree, offering no support for the hypothesis that a redundant adrenergic system may replace the cholinergic system during the development of tolerance to DFP. In contrast to these various negative findings, pilocarpine was less effective in suppressing the responding of rats tolerant to DFP than that of control subjects. This confirms other evidence indicating that a decreased sensitivity of cholinergic (muscarinic) receptors is one mechanism underlying the development of tolerance to DFP.