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Patterns of neural and behavioral activity in freely-moving Navanax inermis (Mollusca; Opisthobranchia).

As part of an ongoing neuroethological study of complex behavior in the opisthobranch mollusc, Navanax inermis, I have extended the available gross anatomical descriptions and used cuff electrodes to obtain chronic recordings from whole nerves or connectives. The major anatomical findings concern a) finer branches of the pedal nerves, particularly P3C P4 and P5; b) the distribution of nerves from the abdominal and subintestinal ganglia; and c) a possible neurohaemal area of the supraintestinal ganglion. With cuff electrodes it has been possible to get good quality recordings (often with spikes in the mv range) during the full repertoire of sexual, predatory and cannibalistic behaviors. The high degree of cryptic neural activity and the fact that in Navanax behaviors are not mutually exclusive, make it difficult to identify one-to-one correspondences between behaviors and neural patterns, However, there is an apparent correlation between the activity of a very large unit(s) on P5 and an exploratory behavior, the Face-Down head posture when it is directed at the substrate rather than prey, or a conspecific.

Animals↗

Melatonin as an anxiolytic in rats: time dependence and interaction with the central GABAergic system.

Anxiolytic and pro-exploratory melatonin properties were assessed in rats using a plus-maze procedure. Both melatonin (1 mg/kg) and diazepam (0.5 mg/kg) showed a significant diurnal variation to decrease anxiety and to promote exploratory behavior. Melatonin displayed anxiolytic activity at night, with absence of effects at noon and a weak activity at the beginning of the light phase. Melatonin pro-exploratory activity was found only at night. Diazepam exerted significant anxiolysis during the night, with less activity during the day. Diazepam pro-exploratory activity was found during the night only. A dose-response study carried out by injecting 1-20 mg/kg melatonin at 12:00 or 18:00 h indicated that melatonin activity was greatest at 18:00 h. Diazepam was anxiolytic at both times, and pro-exploratory at 18:00 h only. Melatonin activity was blunted by administration of the benzodiazepine antagonist, flumazenil.

Analysis of Variance↗

Effects of posttraining ethanol on an appetitive task.

The present study examined the effects of posttraining ethanol administration upon retention of an appetitive task using a variety of retention behaviors associated with the task. Male C57BL/6J mice were individually trained to find a cheese pellet placed in the corner of an open field. Five behavioral measures were used including locomotor activity counts, rearings, grooming episodes, approaches to the cheese pellet, and latency to consume the cheese pellet. Immediately after training, mice were injected intraperitoneally with saline or 2.0 g/kg of ethanol and then returned to their home cage in which four "intruder" mice were added for 2 h after training. On subsequent testing days (1, 6, 14, and 51 days posttraining), mice were returned to the original training environment and the five behaviors were measured. Both saline- and ethanol-treated mice habituated to the initially novel test environment at similar rates as indicated by decreased exploratory behavior (locomotor activity and rearings). In contrast, a divergence in the latency to consume the cheese pellet was observed: Saline-treated mice behaved as though the cheese was rewarding (decreased latency to eat the pellet), while the ethanol group behaved as though the cheese was aversive (increased latency to eat the pellet). Taken with previous studies, these results demonstrate that posttraining ethanol can have strikingly different effects on retention depending on the task, the measure of retention used, and the underlying neural structures involved.

Animals↗

Behavior and electrical brain stimulation in the green iguana, Iguana iguana L. II. Stimulation effects.

Behavioral responses were electrically elicited in the brains of 21 green iguanas. At 518 stimulation sites, a limited number of behaviors could be reliably elicited. Except for some motor responses which had a forced appearance, they corresponded to the basic activity of green iguanas, exploratory behavior, display, defensive and escape-related behavior. Head-nodding displays were reliably elicited post stimulation when imminent escape was prevented experimentally but rarely during stimulation. Goal-directed behavior, i.e., feeding, drinking, mating and fighting behavior, were not elicited. The stimulation sites of frequently elicited behavioral responses revealed regional differences and some structural correlations. The majority of sites yielding defensive display responses were found in the hypothalamus, while dewlap display was more readily and widely elicited. Axial rotation and head-raising were elicited in a ventrothalamic zone extending into the tegmentum mesencephali. Tongue-flicking response sites were mostly concentrated in ventromedial areas of the tel-, di- and mesencephalon. Most escape-related responses were distributed unspecifically but the sites of violent flight responses were confined to the dorsal and lateral mesencephalon.

Animals↗

Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress-related mental illness.

Research in chronic stress has been hampered by the absence of an operational definition for that condition. To explore possible criteria for chronic stress, we repeatedly exposed rats to 2 hr of tail shock per day. After several days, we found elevated prestress corticosterone levels and abnormal behavior, including decreased food consumption, fear-like suppression of activity immediately before stress, greater hesitancy to drop from a suspended wire, and decreased exploratory behavior in a novel environment. A less intensely stressed group of rats also had elevated prestress corticosterone levels, but not the abnormal behaviors that persisted in shocked rats after the stress sessions were discontinued. We propose that abnormalities in both adrenocortical function and behavior are a better marker for chronic stress than abnormalities in either of these systems alone. The animal model we have described may be useful for studying factors that contribute to development of chronic stress or PTSD.

Adrenal Cortex↗

Longitudinal study of daily variation of rats' behavior in the elevated plus-maze.

We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1). a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2). light/dark phases differences in EPM exploration were present at all developmental stages, (3). older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4). behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm.

Aging↗

Differences in learning between hyperprolinemic mice and their congenic controls.

These experiments expanded earlier work on hyperprolinemic mice which showed learning deficits. The following behavioral tasks were used: step-through, passive avoidance; T-maze acquisition; shuttlebox acquisition, and radial-arm maze. Mouse species included PRO/Re-bb (genetically hyperprolinemic mice) and PRO/Re-aa (congenic nonhyperprolinemic controls) obtained from the Jackson Breeding Laboratories. Hyperprolinemic mice were impaired in acquiring T-maze and shuttlebox footshock avoidance behavior. One-trial passive avoidance behavior did not clearly differentiate between the groups. Radial maze performance was poor in both groups due possibly to observed acrophobia and lack of exploratory behavior. The results of this study combined with previously published work suggest that high-brain proline in conjunction with other amino acid changes account for the learning deficits.

Amino Acid Metabolism, Inborn Errors↗

Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits.

Brain development and function are dependent on thyroid hormone (T3), which acts through nuclear hormone receptors. T3 receptors (TRs) are transcription factors that activate or suppress target gene expression in a hormone-dependent or -independent fashion. Two distinct genes, TRalpha and TRbeta, encode several receptor isoforms with specific functions defined in many tissues but not in the brain. Mutations in the TRbeta gene cause the syndrome of peripheral resistance to thyroid hormone; however, no alterations of the TRalpha gene have been described in humans. Here we demonstrate that mice lacking the TRalpha1 isoform display behavioral abnormalities of hippocampal origin, as shown by the open field and fear conditioning tests. In the open field test mutant mice revealed less exploratory behavior than wild-type mice. In the contextual fear conditioning test mutant mice showed a significantly higher freezing response than wild-type controls when tested 1 week after training. These findings correlated with fewer GABAergic terminals on the CA1 pyramidal neurons in the mutant mice. Our results indicate that TRalpha1 is involved in the regulation of hippocampal structure and function, and raise the possibility that deletions or mutations of this receptor isoform may lead to behavioral changes or even psychiatric syndromes in humans.

Animals↗

Spatiotemporal properties of layer V neurons of the rat primary somatosensory cortex.

Animals in their natural environments actively process spatiotemporally complex sensory signals in order to guide adaptive behavior. It therefore seems likely that the properties of both single neurons and neural ensembles should reflect the dynamic nature of such interactions. During exploratory behaviors, rats move their whiskers to actively discriminate between different tactile features. We investigated whether this dynamic sensory processing was reflected in the spatial and temporal properties of neurons in layer V of the 'whisker area' in the rat primary somatosensory cortex. We found that the majority of layer V neurons had large (8.5+/-4.9 whiskers) spatiotemporal receptive fields (i.e. individual cells responded best to different whiskers as a function of post-stimulus time), and that the excitatory responses of surround whiskers formed a spatial gradient of excitation that seemed to reflect the greater use of the ventral and caudal whiskers during natural behaviors. Analyses of ensembles of layer V neurons revealed that single-whisker stimuli activated a portion of layer V that extends well beyond a single cortical column (average of 5.6 barrel cortical columns). Based on these results, we conclude that the rat primary somatosensory cortex does not appear to operate as a static decoder of tactile information. On the contrary, our data suggest that tactile processing in rats is likely to involve the on-going interactions between populations of broadly tuned neurons in the thalamocortical pathway.

Animals↗

Modulatory effects of galanin in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress.

The neuropeptide galanin has been identified as a possible neurotransmitter/neuromodulator within the central nervous system. In the present study, a potential role for galanin in the lateral bed nucleus of the stria terminalis (BSTL) in modulating behavioral and neuroendocrine responses to an acute stress was investigated. In the first experiment, acute immobilization stress induced anxiety-like behavioral responses in rats, measured on the social interaction and elevated plus-maze tests. Immobilization stress decreased both social interaction time and open arm exploratory behavior on the elevated plus-maze. Bilateral administration of the galanin antagonist M40 (1.0 nmole/0.2 microl) into BSTL immediately prior to stress exposure attenuated the anxiogenic-like effects of immobilization stress, restoring both social interaction time and exploration of open arms to control levels. Administration of the antagonist alone had no effect on baseline behavior of unstressed control rats in either test, suggesting that the modulatory effect of galanin elicited during stress is not exerted tonically in unstressed animals. In the second experiment, immobilization stress produced an increase in plasma adrenocorticotropic hormone (ACTH) that was also attenuated by bilateral administration of M40 into BSTL prior to stress. These results suggest that during stress, the neuropeptide galanin exerts a modulatory effect in the BSTL, facilitating behavioral and neuroendocrine components of the acute stress response.

Animals↗

Effect of an adenosine antagonist and an adenosine agonist on status entry and severity in a model of limbic status epilepticus.

Adenosine is an endogenous neuromodulator that suppresses excitatory neurotransmission. We postulated that adenosine-mediated mechanisms resist status epilepticus (SE) entry and limit SE severity. In the first experiment rats were given an adenosine agonist (2-chloroadenosine), an adenosine antagonist (aminophylline), or saline vehicle, prior to SE induction with pulsed-train current delivered to amygdala in successive 5-min current-on sessions. Saline-treated animals entered limbic SE, with predominantly exploratory behavior, after 6.0 +/- 0.9 current-on sessions. Aminophylline increased major convulsive activity during stimulation and resulted in entry into convulsive SE after only 2.1 +/- 0.1 sessions. 2-Chloroadenosine, in contrast, suppressed major convulsive activity during stimulation, and blocked (in 3/7) or delayed (4/7) SE entry, with successes requiring 12.8 +/- 0.9 stimulation sessions. In a second experiment, animals already in exploratory SE were administered a single injection of saline vehicle, aminophylline, or 2-chloroadenosine. Aminophylline converted exploratory SE into lethally severe convulsive SE. 2-Chloroadenosine suppressed SE behaviorally and electrographically, and protected recipients from the seizure-associated cerebral damage seen in saline-administered SE controls. These results support the hypothesis that endogenous adenosine mechanisms resist SE entry, modulate the severity of ongoing SE, and limit the anatomic spread of seizure activity.

2-Chloroadenosine↗

Schedule-induced polydipsia: attenuating effects of decreased size of food granulations.

The effect of food texture on the development of schedule-induced polydipsia was examined in six groups of rats (n = 8), each receiving one of six grades of food granulation. A seventh group received pellets. By the end of 15 sessions of FT 60-sec food delivery, rats receiving pellets and the coarser granulations had developed polydipsia. The volume of water drunk at asymptote by the remaining groups declined with decreased coarseness of the food. Ethological analyses of the behavioral repertoire of the rats during the fifteenth session showed that the polydipsic groups sustained their drinking throughout the session, rather than turning from ingestive to exploratory behaviors near the end of the session, as was the case with animals receiving finer granulations. The enhanced drinking induced by the coarser food texture was reciprocally related to the amount of time the animal spent with its head in the feeder hole during the period of maximum drinking. The results support the conclusion that the schedule-induced polydipsia traditionally demonstrated with pellets as the reinforcer is critically dependent on the fact that pellets are coarse in texture.

Animals↗

Age differences in the ability of chimpanzees to distinguish mirror-images of self from video images of others.

To evaluate Heyes's (1994) claim that chimpanzees are incapable of using mirrored information to obtain otherwise unavailable information about the self, we exposed two different age groups of chimpanzees (3-year-olds and 7- to 10-year-olds) to mirrors and video images of conspecifics. Their reactions to these stimuli were videotaped and were later scored for behavioral indices of self-recognition by a trained observer who was blind to the purpose and conditions of the study. Some types of behavior (contingent facial and body movements) were clearly influenced by the type of stimulus that the chimpanzees were viewing but not by age; however, other behaviors (self-exploration) were affected by age in conjunction with the type of stimulus the animals were viewing. The results suggest that, unlike self-exploratory behavior, contingent facial and body movements may not, by themselves, be reliable indicators of self-recognition.

Aging↗

Dopamine in the lateral hypothalamus may be involved in the inhibition of locomotion related to food and water seeking.

Experiments were conducted in male rats to assess the motor effects of bilateral intraperifornical microinjections of sulpiride, dopamine (DA) and other drugs. Sulpiride increased locomotion of the animals in all the experiments reported here. DA (10 micrograms) administered 5 minutes before sulpiride (8 micrograms) reduced the motor stimulant effect of the neuroleptic from 1601.3 +/- 337.6 to 742.5 +/- 180.4 counts/30 min. SCH 23390 (15 micrograms), haloperidol (2.5 micrograms) and atropine (18 micrograms) did not modify the locomotion level of animals acclimated to the actimeters. After carbachol (5 micrograms) the animals attained a level of hyperactivity (1459.5 +/- 146.5 counts/30 min) similar to that induced by sulpiride (1595.7 +/- 365.7 counts/30 min) in the same experiment. In other experiments DA (10 micrograms) administered 30 min before sulpiride again blocked the effect of 8 micrograms of sulpiride, and reduced the initial hyperactivity of food- and water-deprived animals previously familiarized with the actimeters (922.4 +/- 49.38 counts/15 min under saline, vs. 544 +/- 29 counts/15 min under DA). The same DA dose did not modify the initial spontaneous activity of nonfamiliarized nonfood-deprived rats (508.9 +/- 96.1 after saline vs. 520.9 +/- 47.1 after DA). These results suggest the presence of cells in the lateral hypothalamus involved in the control of locomotion. These experiments also suggest that locomotion triggered by the LH may be exploratory behavior essential to the search for water and food. As a corollary, DA in the LH appears to be involved not only in the inhibition of feeding and drinking but also in the inhibition of exploratory and food- and water-directed locomotion.

Animals↗

Lasting behavioral effects after treating rats with CGS 8216 on postnatal days 9 to 21.

The lasting effects of chronic exposure to CGS 8216 in early postnatal life were studied in the social interaction test of anxiety, the holeboard test of exploratory behavior, a startle test and on convulsions induced by pentylenetetrazole. Male rat pups were treated with CGS 8216 (10 or 20 mg/kg/day) from postnatal day 9 until weaning (day 21), and tested in adulthood. In the social interaction test, the pups that had been exposed to CGS 8216 during development showed increased social interaction in both unfamiliar and familiar test conditions, (particularly the latter), in contrast to the decrease in social interaction that results when CGS 8216 is given acutely to adult animals. Conversely, the developmentally-treated rats were more sensitive to the convulsant effects of pentylenetetrazole, and this effect is in the same direction as that seen in adults after acute administration. No effects of the early treatment were detected in adult animals in the holeboard or startle tests.

Animals↗

[Psychotropic effects of diazepam in male mice with alternative psycho-emotional statuses].

Effects of diazepam (0.1, 0.5 and 1 microg/kg, i. p.) on communicative, anxious behaviors, exploratory activities and sexual motivation of C57BL/6J male mice with alternative psychoemotional statuses (intact and anxious) were studied. Increased level on anxiety was formed by sensory contacts technique. Behavioral effects of diazepam depend on initial psycho-emotional status of animals. The compound has an anxiolytic effect in new situation on anxious males but does not have it in situation of social contacts. Diazepam reinforces initial sexual interest in anxious mice; however, it does not enable correct exhaustion of sexual motivation. Furthermore, the compound provokes development of the exhaustion in intact male mice.

Animal Communication↗

Increased ethanol self-administration and anxiety-like behavior during acute ethanol withdrawal and protracted abstinence: regulation by corticotropin-releasing factor.

BACKGROUND: Animal models of alcohol dependence suggest that long-term alterations in brain corticotropin-releasing factor (CRF) systems, key mediators of the behavioral stress response, may be involved in the development and reinstatement of dependence on drugs of abuse. The objective of the present study was to investigate the role of CRF in the regulation of ethanol self-administration and to examine the behavioral stress response during acute withdrawal and protracted abstinence. METHODS: Male Wistar rats were made dependent on ethanol via chronic exposure to ethanol vapor. Ethanol self-administration and exploratory behavior in the elevated plus maze were measured at 2 hr and 3 to 5 weeks after exposure. The role of CRF in ethanol self-administration was examined via central injection of the CRF receptor antagonist D-Phe-CRF(12-41). RESULTS: Rats showed increased responding for ethanol 2 hr and 3 to 5 weeks after chronic ethanol exposure, which was attenuated by central injection of D-Phe-CRF(12-41). In addition, rats displayed a decrease in open-arm exploration in the elevated plus maze when tested 2 hr and 4 weeks after exposure. CONCLUSIONS: These results indicate that chronic ethanol exposure leads to increased ethanol self-administration and decreased open-arm exploration in the elevated plus maze during acute withdrawal and protracted abstinence. Attenuation of ethanol self-administration via central injection of D-Phe-CRF(12-41) implicates CRF as an underlying mechanism regulating long-term motivational effects associated with alcohol dependence.

Alcohol Drinking↗

Multiple roles for dopamine in Drosophila development.

Manipulation of dopamine levels by inhibition of tyrosine hydroxylase activity was accomplished in Drosophila melanogaster larval instars by feeding enzyme inhibitors for a 24-hr period. Behavioral assays performed immediately after treatment demonstrated that larval phototaxis, salt aversion, and heptanol preference were unaffected by reduced levels of dopamine. Within a few hours of treatment, the larvae ceased exploratory behavior and were unresponsive to external stimuli; these larvae eventually died. This behavior is strikingly similar to that displayed by dopamine-deficient transgenic mice. Treated larvae placed immediately onto normal food (to replenish dopamine levels) showed significant developmental delays and decreased fertility as adults. The lethality, developmental retardation, and decrease in fertility were reversed by addition of L-DOPA to inhibitor-containing food, suggesting that these effects were due solely to inhibition of tyrosine hydroxylation. Depletion of dopamine in newly eclosed females resulted in abnormally developed ovaries. These results suggest that the enzymatic function of tyrosine hydroxylase is vital and that reduced levels of dopamine result in akinesia and lethality, developmental retardation, and decreased fertility.

Animals↗