Neuroactive steroids modulate crustacean locomotor activity.

We examined the effects of neuroactive steroids known to modulate gamma-aminobutyric acid(A) (GABA)(A) receptor activity, on locomotor activity in a submerged circular open-field apparatus. Juvenile male lobsters, Homarus americanus, were treated with a single administration of an agonist, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, 3alpha,5alpha-TH PROG), an antagonist, pregnenolone sulfate (PREGS), or vehicle alone. 3alpha,5alpha-TH PROG treatment (125 and 250 microg) significantly reduced while PREGS significantly elevated locomotor activity in a dose-dependent manner similar to diazepam. PREGS increased locomotor activity at 30 and 60 microg, while diminishing such activity and altering locomotor patterns at 120 microg. These results suggest that neuroactive steroids may affect crustacean GABA receptors in a fashion similar to the GABA(A) type found in the vertebrates, and that they may be involved in the regulation of locomotor behavior.

Effects of exogenous serotonin on a motor behavior and shelter competition in juvenile lobsters (Homarus americanus).

Three experiments were conducted to determine (1) the pharmacodynamics of 5-hydroxytryptamine in juvenile lobsters; (2) the effects of 5-hydroxytryptamine, using a range of dosages, on a motor behavior used to escape an aversive situation; and (3) the effect of doses that did and did not inhibit this motor behavior on measures of dominance and shelter competition. The fate of 5-hydroxytryptamine in hemolymph over a 60-min post-injection period showed that the concentration fell rapidly to a low plateau that was maintained for at least 1 h. Low doses of 5-hydroxytryptamine did not affect locomotor behavior, but higher doses inhibited it. Dominance and subsequent possession of a shelter were unaffected by a low dose of 5-hydroxytryptamine but a higher dose that inhibited locomotion resulted in lobsters that lost fights and did not secure or retain possession of the shelter. In the context of dominance and shelter competition, we were unable to demonstrate any advantage of the low dose of exogenous 5-hydroxytryptamine and a severe disadvantage with the higher dose. Previous reports of transient increases in aggression in 5-hydroxytryptamine-treated subordinate lobsters did not take into account motor inhibition as a possible critical variable in aggression.

Human fetal heart rate dishabituation between thirty and thirty-two weeks gestation.

Few studies of human fetal habituation have included dishabituation procedures (i.e., assessment of the reemergence of a habituated response) to determine if response decrements are the result of reevaluation of information (a brain process) or fatigue of peripheral receptors. The purpose of this study is to describe the ability of the human fetus to learn and recall information with procedures to assess the central nervous system. Fetal heart rate (FHR) of 84 fetuses between 30 and 32 weeks gestational age was examined in response to 3 series of vibroacoustic (VA) stimuli presented at pseudorandom intervals of 25-45 s over the head of the fetus. Responses to the first series of 15 stimuli (S1) were compared with an identical second series of 15 stimuli (S1) presented over the head of the fetus. Between the 2 series, a novel (dishabituating) VA stimulus (S2) was presented, differing from S1 in intensity and frequency. The third series of S1s was applied to the mother's thigh as a control for possible maternal responses to the stimulus. Prestimulus FHR was computed during a 5 s interval before each stimulus, and mean FHR was computed during the intertrial interval (average FHR). The response to S1 during the first series of trials (1-15) produced a sustained rise in both prestimulus and average FHR, r(83) = .90, p < .001. After the novel S2 (trial 16) the rate of change was attenuated for average FHR, r(83) = .12, ns, to S1 for trials 17-31 but not prestimulus FHR, r(83) = .50, p < .001. The decrease in FHR response was reestablished when stimulation was applied to mother's thigh, trials 32-41, r(83) = .92, p < .001. A significant habituation pattern across trials was observed for the first series of S1s when prestimulus HR was subtracted from each preceding average FHR value (delta FHR). After the single novel stimulus (S2), the FHR response to S1 reemerged. All combinations of beginning and ending series slopes were compared, and only the rate of change during the last 4 trials of the initial presentation of S1 and the first 4 trials after the novel stimulus was significant, F(1, 82) = 9.21, p < .003. Uterine contractions collected from the continuous record were not related to the presentation of the novel stimulus, chi 2(1, N = 84) = 0.59, p < .50, ns, or delta FHR slope after the novel stimulus, chi 2(9, N = 84) = 10.52, p < .50, ns. These results established that the 32 week human fetus is capable of detecting, habituating, and dishabituating to an external stimulus and support the premise that areas of the human fetal central nervous system critical for detecting and discriminating information and for learning and memory have developed by the early third trimester.

Cocaine exposure prebreeding to weaning: maternal and offspring effects.

In a model emphasizing prebreeding cocaine administration, rats exposed to cocaine (50 mg/kg) daily were compared to saline-injected and noninjected controls with respect to weight changes, food and water intake, maternal behavior, offspring weight, and activity. During the first 21 days cocaine-treated dams lost weight, while the control dams gained. Throughout gestation and the first 14 days of lactation all groups gained weight, but the cocaine-exposed dams never completely recovered from the initial anorectic effect. Except during the first week of exposure, cocaine dams ate and drank more than the normal controls and drank more than the saline group. During gestation there was no difference in food intake, although the cocaine dams continued to drink more than controls. During lactation there were no differences in food and water consumption across groups. However, the cocaine dams exhibited more nursing behavior. From birth to day 21, the offspring of cocaine-treated dams were smaller than those of either control group. By 51 days of age, group differences had disappeared. Cocaine-exposed pups and saline offspring tested at days 28 and 85 were more active than those of noninjected controls. The results indicate that administration of cocaine for a period prior to breeding and during gestation and lactation, a protocol which closely resembles human drug abuse patterns, is more devastating than the administration during gestation.

Perinatal cocaine exposure and functional brainstem development in the rat.

Rat pups exposed to cocaine via maternal intromission throughout gestation and lactation displayed significantly prolonged auditory brainstem response component latencies and interwave intervals. Longitudinal analysis revealed that this effect was most pronounced on the 22nd postnatal day. Increasing the rate of stimulation further impaired neurosensory transmission in the caudal auditory pathway. These results indicate that both axonal and synaptic events may be affected to some degree and the timing (age) of optimum cocaine influence suggests that delayed myelination may be involved. The corresponding retardation in general development of the cocaine exposed pups further implicates maternal, fetal and postnatal utilization of nutritional resources as the basis for this outcome.

Individual behavior differences related to induced tumor growth in the female Syrian hamster: two studies.

The relationship of individual behavioral differences to induced tumor growth and to Natural Killer (NK) cell activity was investigated in the Syrian hamster in the context of a long-term natural stressor (group social interaction). In the first sub-experiment, 90-day-old females had blood drawn for NK cell assays. Animals were then placed in groups of ten, and two samples of behavior were obtained on videotape. All hamsters were injected midback subcutaneously with malignant melanoma, developed tumors, and were sacrificed 35 days later. Eight reliable behaviors were coded from the videotapes and were factor analyzed, yielding two factors: "Activation" and "Inactivity." The first factor of "Activation" was correlated p less than .06, two-tailed) with autopsy tumor size. The experiment was repeated using females aged 210 days. Factor analysis generated two factors virtually identical to those previously found. The factor of "Activation" was again correlated with autopsy tumor size (p less than .05, one-tailed). For older animals only, the second factor of "Inactivity/dominance" was associated with higher NK cell activity for one of the two samples. A second study was conducted in order to replicate the factor structure of the first two sub-experiments, as well as the relationships of behavioral variables to tumor outcome variables. However, the design differed mainly in taking four rather than two samples of behavior; and in using as an outcome measure time to detection of palpable tumor, rather than autopsy tumor size. The factor analysis derived very similar factors. The second factor of "Inactivity" was correlated significantly (p less than .007, two-tailed) with tumor latency, which is congruent with the previous results. Overall, the results showed that: (a) individual behaviors in hamsters can be rated reliably, and cluster repeatedly across independent studies into certain patterns; and (b) the pattern interpreted as "Activation" was associated with poorer tumor outcome relative to the pattern of "Inactivity-(dominance)."

Bioassayable cholecystokinin in the brain of the goldfish, Carassius auratus.

Cholecystokinin (CCK)-gastrin peptides are shown to be present in the brain of all the species ranging from coelenterates to mammals. Differentiation between CCK and gastrin, presumed to be evolved from a common ancestral cerulein-like peptide, has been suggested to occur at the level of the amphibians. We examined the presence of bioassayable CCK, as determined by its potency to stimulate enzyme secretion from isolated rat pancreatic acini, in the brain of the goldfish Carassius auratus, a more primitive vertebrate than the amphibian. Among the various regions tested, the brain stem, telencephalon and spinal cord possess the highest levels of bioassayable CCK followed in decreasing order by gustatory lobes, optic tectum and duodenum. No detectable levels of CCK were found in the cerebellum. The observed bioactivity was not due to gastrin because: radioimmunoassay of the brain homogenates for gastrin revealed very low or nondetectable levels of gastrin; amylase release dose-response curves for standard CCK8 and the brain homogenate were identical; and proglumide, a competitive antagonist of CCK8, inhibited homogenate CCK-induced enzyme release with a parallel rightward shift in the dose-response curve. These observations provide evidence for the distinct presence of CCK in the brain of the goldfish suggesting that the differentiation of CCK as a distinct neuropeptide, from that of gastrin, occurs at the level of Osteichthyes (bony fish).

Prior stress and behaviorally conditioned histamine release.

Male guinea pigs were either handled ('stressed') or not disturbed ('non-stressed') for four weeks prior to conditioning with a classical discrimination conditioning design. Animals were sensitized to bovine serum albumin (BSA) and four weeks later presented with either an odor (the CS+) paired with BSA or a second odor (the CS-) paired with saline. These pairs were presented in a random order for ten trials. Weekly blood samples were assayed for histamine and cortisol levels. Following the conditioning trials, animals were subjected to extinction trials during which the CS+ odor was presented but not paired with the BSA. The animals handled prior to the conditioning procedures learned the association between the odor and the BSA as indicated by increased histamine levels when exposed to the conditioned odor alone. The non-handled group did not learn. Additionally, the cortisol levels were significantly higher for the handled group vs. the non-handled group when the CS+ was presented during extinction. The role of stress in both learning and immunomodulation is discussed.

Stress-behavior interactions in hamster tumor growth.

The aim of this study was to investigate the effects of a mechanical stressor and individual behavior differences (separately and in combination) on tumor development in the female Syrian hamster. Studies by other investigators have documented the tumor-enhancing effects of such mechanical stressors as rotational stress. Previous studies by our group found that both size of tumor and time to tumor detection were significantly related to a dimension we call "activation." Eighty 100-day old female Syrian hamsters were placed in circular plexiglas environments in groups of 10. Nineteen days after introduction to the cages, a stress condition was imposed on half the animals (four cages). This consisted of shaking each cage of animals three times a week for three 10-minute intervals. Each group's behavior was videotaped in multiple samples to document pre- and poststress behaviors. Twelve days after the stress condition was initiated, each animal was injected subcutaneously midback with one melanoma tumor fraction. Animals were palpated every three days to determine time to detection of tumor. The videotaped behavior samples were coded for behaviors associated with "activation," inactivity, and interaction. Factor analysis resulted in basically the same first factor of activation found in our previous studies. Hamsters in the nonstressed groups had a significantly longer time to tumor development than those in the stressed groups (22.5 days vs. 12.6 days, p less than 0.005). While no prestress behaviors were associated significantly with time to tumor detection, the poststress activation factor was significantly correlated with longer time to tumor development in the stressed group (r = .61, p less than 0.0001). These results suggest that while the stress condition is more powerful than prestress individual behaviors in affecting the outcome variable, stress appears to interact with the individual behaviors related to "activation" to mitigate the negative effects of stress on tumor growth.

Habituation and cortisol dysregulation in depression.

The relationship between hypothalamic-pituitary-adrenal (HPA) dysregulation and skin conductance measures of habituation, stimulus specificity, and dishabituation was investigated in psychiatric patients exhibiting depressed affect. As a group, depressed patients showed a relative failure to dishabituate when compared with control subjects. Nonsuppression of cortisol following dexamethasone was associated with decreased response specificity as reflected in direct response measures and baseline skin conductance level. The impairment of response specificity to a novel stimulus is consistent with previous studies demonstrating a role for cortisol in the regulation of selective attention processes.

Learned histamine release.

Most of the effort directed at understanding the problems of allergy has focused on the interacting components of the immune system. The possibility that histamine may be released as a learned response has now been tested. In a classical conditioning procedure in which an immunologic challenge was paired with the presentation of an odor, guinea pigs showed a plasma histamine increase when presented with the odor alone. This suggests that the immune response can be enhanced through activity of the central nervous system.

Sex differences and asymmetries of catecholamines: relation to turning preferences.

Male and female Sprague-Dawley rats were tested for turning preferences in a multiple alley maze. The left and right caudate-putamen were dissected and assayed for norepinephrine and dopamine. Dopamine was not found to be lateralized contralateral to turning preference for females as a group. However, dopamine was significantly lateralized contralateral to the females turning preference if a strong turning bias was present. No relationship between dopamine asymmetry and turning preference was evident for males. Females were found to have norepinephrine significantly lateralized to the left caudate-putamen; in males greater striatal norepinephrine levels were equally distributed between left and right sides. This sexual dimorphism in norepinephrine lateralization was not related to turning preference.

Attention, memory, and cigarette smoking.

Four experiments tested the effects of smoking one cigarette on verbal memory and attention. In Experiment I, 18 men were tested under three conditions in a repeated-measures design (pretrial smoking, posttrial smoking, no smoking). Recall of a 50-word list was tested immediately and after intervals of 10 and 45 min. Pretrial smoking resulted in improved recall 10 and 45 min after learning, but not immediately. Posttrial smoking was ineffectual. In Experiment II, three posttrial smoking intervals (1, 5, and 30 min after presentation of a 20-word list) were compared with pretrial smoking and no smoking using a between-subjects design. The 76 light, moderate, and heavy smokers in Experiment II smoked a 1.38 mg nicotine cigarette and were tested 24 h later. Improved recall occurred for pretrial smoking, but not for any posttrial smoking interval and for light and moderate smokers only. Experiment III compared a low (0.40 mg) and high (1.38 mg) level of nicotine cigarette in light and heavy smokers using pretrial smoking. The high-nicotine cigarette resulted in improved recall for both immediate- and delayed-recall tests. The low-nicotine cigarette was less effective. Light and heavy smokers differed in effect of smoking on heart rate, but not in effect of smoking on recall. Experiment IV found no effect of smoking on depth of processing. The possible mechanisms by which nicotine affects recall are discussed.

Habituation, sensitization, and redirection of aggression and feeding behavior in the three-spined stickleback (Gasterosteus aculeatus L.).

Three-spined stickleback males maintained in individual aquaria built nests and defended the entire aquarium as a territory. Adjacent compartments containing another male stickleback, a gravid female, or a nongravid female provided a social context within which to study the habituation and sensitization of aggression elicited by a conspecific male intruded into the subject's territory. Typical sensitization-habituation curves were found for all fish regardless of the kind of neighbor. However, behavior redirected as a result of the stimulation of the intruded male differed between conditions. The group with a male neighbor showed increased aggression toward the neighbor, the group with a gravid female neighbor showed courtship, and the group with nongravid female showed neither. A third behavior, nest building, showed no difference between conditions, a result providing little evidence for a simple explanation in terms of general arousal. A second experiment elicited the same motor response to the intruded stimulus, but the motivational category was changed by eliciting the behavior by presenting live brine shrimp. In this experiment, aggression did not change during habituation, but the waning predation was redirected to another food-securing behavior, picking at the substrate. The results provide evidence for the important role that social context plays in understanding the redirection of behaviors, a phenomenon predicted from an extension of the dual-process theory of habituation.

Down syndrome individuals fail to habituate cortical evoked potentials.

Small sample cortical evoked potentials in response to repetitive auditory stimuli were recorded from 10 Down syndrome individuals and from 10 nonretarded persons whose initial evoked potential amplitude was equated with that of the Down syndrome subjects in a matched-pairs experimental design. Regression analysis of sequential evoked potential amplitude revealed that the nonretarded subjects showed rapid habituation of their cortical evoked potentials whereas the Down syndrome subjects failed to show habituation. The findings support the concept of a deficit in inhibitory capacity at the fundamental electrophysiological level as a substrate for the behavioral-cognitive impairment characteristic of Down syndrome individuals.

Dietary ferulic acid, biochanin A, and the inhibition of reproductive behavior in Japanese quail (Coturnix coturnix).

A study was conducted to determine the effects to two dietary compounds, biochanin A and ferulic acid, on the reproductive performance of Japanese quail, Coturnix coturnix. These compounds may be present in the diet of wild birds during dry years or at the end of the growing season during normal years. Four treatment groups, each fed a diet supplemented with biochanin A or ferulic acid, and a control group were tested for morphological and behavioral effects before, during and after treatment. Fertility and hatchability data were collected during treatment only. Ferulic acid was shown to inhibit male copulatory behavior during treatment. Biochanin A inhibited male copulatory behavior during and after treatment. Neither drug affected female copulatory behavior though egg-laying was inhibited by the low dose of biochanin A. Ferulic acid significantly reduced the hatchability of eggs. Biochanin A increased the fertility of males and the hatchability of eggs fertilized by them. A correlation between results of this study and natural conditions of reproduction is discussed. It is concluded that both biochanin A and ferulic acid exert inhibiting influences on the reproductive behavior of Coturnix.

Panic and generalized anxiety disorders. Developmental antecedents and precipitants.

Seventeen subjects with panic disorder (PD) and 16 subjects with generalized anxiety disorder (GAD) were interviewed to obtain their developmental and psychiatric histories. The groups reported a similar incidence of early separation, separation disorder in childhood, and separation causing exacerbation of symptoms. The groups differed significantly in that those with PD had a higher incidence of a grossly disturbed childhood environmental and major depressive episodes. The results of this preliminary study support the validity of the DSM-III distinction between PD and GAD.