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Exploration is an essential, life-preserving component of animal higher nervous functions. The experiments presented here show that exploratory behavior may differ in relation to the subject's emotional baseline, and that accordingly it is affected differently by various antidepressants.
Corticotropin-releasing factor (CRF) administered intracerebroventricularly (ICV) to rats and mice has been shown to elicit a variety of behaviors resembling those that occur in stress. In a novel multicompartment chamber, ICV CRF altered the behaviors in a manner closely resembling that observed following a period of restraint. In particular, 75 ng CRF ICV or 30-40 min restraint markedly reduced the time mice spent in contact with novel stimuli. ICV injections of a peptide antagonist of CRF, alpha-helical CRF9-41 (ahCRF), reversed the effects of restraint on this measure. This effect of ahCRF was dose dependent, with a minimal effective dose of 10 micrograms. Other behavioral measures appeared normal, and ahCRF did not significantly alter the stimulus-contact time in unrestrained mice. These results provide strong evidence to support the hypothesis that endogenous CRF may be a factor affecting stress-induced changes in exploratory behavior in mice.
Rats tested for 1 h in the Behavioral Pattern Monitor (BPM) after injection of the mixed serotonergic agonist d-lysergic acid diethylamide (LSD) exhibit a behavioral profile similar to that produced by various hallucinogenic 5HT-2 agonists. The characteristic effects of the hallucinogens include suppression of locomotor and exploratory behavior and a preferential decrease in entries into the center of the BPM during the initial half of the test session. After LSD, the initial suppression of responding is followed by a subsequent increase in locomotor activity that is not observed with other serotonergic agonists. In the present studies, the 5HT-1 and beta-adrenergic antagonist d,l-propranolol and the 5HT-2 antagonist ritanserin were administered individually or in combination prior to the acute administration of LSD to test for the involvement of these receptor subtypes in the mediation of the effects of LSD in the BPM paradigm. Propranolol (20 mg/kg) abolished the initial suppression of activity induced by 60 micrograms/kg LSD without affecting the subsequent increase in locomotion. Conversely, 2.0 mg/kg ritanserin failed to block the initial suppressive effects of 60 or 120 micrograms/kg LSD, but attenuated the LSD-induced increases in activity during the second half of the session. The combination of propranolol and ritanserin prevented both these effects of LSD. By contrast, the more selective 5HT-2 agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) (0.27 mg/kg) produced an initial suppression of activity in the BPM that was blocked by 2.0 mg/kg ritanserin and was not followed by a subsequent increase in activity. (ABSTRACT TRUNCATED AT 250 WORDS)
Cerium chloride (1:3 complex with sodium citrate) was administered to male Swiss mice (6 to 8 weeks old) either intragastrically or subcutaneously at the 7 day LD5 or LD25 level. Open field behavior (ambulations, rearings) was quantified and tissue/organ Ce levels determined at 4 hr., 1, 3 or 7 days post administration. Via the i.g. route, Ce was poorly absorbed resulting in no observable behavioral alterations and no correlations between behavior and tissue levels. Via the s.c. route, Ce significantly (p less than 0.05) depressed ambulations and rearings, mainly at short times following administration of the LD25 dose. Analogous findings were obtained in a separate study of exploratory behavior. There was a significant (p less than 0.05) correlation between open field behavior and tissue Ce levels: thus, rearings were inversely correlated with lung, stomach, cerebrum, cerebellum and brain stem Ce levels and ambulations were inversely correlated with liver, kidney, lung, blood, stomach, intestine, muscle, cerebrum, cerebellum and brain stem levels. Spleen Ce levels and ambulations were directly correlated and it is speculated that the spleen may serve a protective function in the case of Ce intoxication.
Mice were maintained at light-dark cycle with lights on from 05:00-19:00 for 10 d in laboratory. The study was performed at 07:00-09:00, 15:00-17:00, and 21:00-23:00 in June and July. Scopolamine (Scop, 0.1 and 0.4 mg.kg-1, ip) was injected 15 min prior to training or the first exploratory test. The amnesic effects of Scop showed hyperresponses at 07:00-09:00 and 15:00-17:00, and hyporesponses at 21:00-23:00 using step-through and step-down tasks. The circadian effects of Scop on exploratory behavior were consistent with the findings above mentioned. The numbers of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites in the temporal cortex and hippocampus were more at 08:00 and 16:00 than those at 22:00. However, muscarinic receptor levels in the striatum were lower at 08:00 than those at 22:00. These results indicated that the effects of Scop on memory, behavior in a novel environment, and muscarinic receptors in brain regions showed circadian changes in mice.
The present study was undertaken to investigate the behavioral effects of postnatal lead exposure. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally daily for 20 days. Control rats received 1 mg/kg sodium acetate, or 8 mg/kg sodium acetate in oversized litters. The high dose lead acetate group and the high dose, oversized sodium acetate group showed impaired weight and length increment during the end of the treatment. Rats treated with the higher dose of lead showed delayed eye opening. The time required to turn in a negative geotaxis test was transiently longer in rats treated with the higher dose of lead. A tendency of reduced forepaw grasping ability was seen in lead-treated rats during the end of the lead exposure. Ambulation and rearing in an open field were lower for the rats treated with the higher dose of lead acetate during certain periods of development. Impaired performance in a balancing rod test was also seen in the rats treated with the higher dose of lead at the adult stage, while no difference was seen in ambulation or gnawing activity during tail pinch-induced stress. Thus, lead intoxication in rats during the early postnatal period, with doses that approximate those in children, induced transient as well as persistent dysfunctions in exploratory behavior and motor skills. These observed actions of lead may be related to impaired maturation of sensitive brain regions which develop postnatally.
Although a large literature has documented the varied effects of stress on an organism, relatively little attention has been devoted to investigating stress effects in ecologically relevant situations. Our experiment was conducted to assess the effects of stress on rats' (Rattus norvegicus) exploration of novel objects in a seminaturalistic and familiar environment that is relatively free of the constraints that have been placed on rats in prior investigations of stress. The results show that prior exposure to stress decreased the rats' diversity of exploration but did not affect general activity in comparison with animals not exposed to stress. We propose that the effect of stress on the qualitative aspects of exploratory behavior may be due to effects on organisms' sensitivity to predation.
Pregnant Long-Evans rats were administered cocaine orally (60 mg/kg) on gestational days 14-21, or subcutaneously (40 mg/kg) on gestational days 8-21. The oral dosage of cocaine produced some maternal lethality and reduced maternal weight gain throughout the pregnancy by approximately 12%. The subcutaneous dosage regimen reduced the lethality but still caused a decrease in maternal weight gain. Neither dosing regimen affected the number of pups in the litter, their weight, or growth. The offspring of dams that received the oral dosage were examined as adults in an automated holeboard apparatus and were also tested at postnatal day 21 and as adults in an open field. Adult animals exposed prenatally to cocaine did not differ from untreated controls in any of the automated measures of the holeboard apparatus or in the various behaviors, including nosepokes, recorded in the open field. Animals in the vehicle control group did make fewer nosepokes in the open field than the cocaine group, which did not differ from untreated animals. The offspring of dams given the subcutaneous dosage regimen were observed in the open field at day 21. In this case, the prenatal cocaine group had a tendency to make fewer crosses into adjacent quadrants, to rear less often, and to make fewer nosepokes than the control groups. Based on these and other data from our lab, it does not appear that in the rat, prenatal cocaine exposure has pronounced effects on subsequent exploratory behavior and activity in weanling or adult animals.
The role of corticotropin-releasing factor (CRF), an endogenous neuropeptide, in modulating species-typical responses was examined in an unfamiliar open field containing a small chamber. Rats placed in this small chamber spent most of their time withdrawn in it. However, rats given an intracerebroventricular injection (20 micrograms) of alpha-helical CRF(9-41), a CRF receptor antagonist, emerged from the chamber and explored the unfamiliar open field. Additional studies showed that after 1 exposure to the test environment, vehicle-treated rats increased their time spent in the open field and returned intermittently to the chamber. This result suggests that reexposure reduces the threatening impact of an unfamiliar open field. Importantly, CRF (300 ng) injected centrally, but not peripherally, before reexposure to the test environment significantly reduced exploration in the open field and increased a pattern of defensive-withdrawal into the chamber. Data suggest that whether defensive-withdrawal or exploratory behavior is exhibited may depend on CRF actions in brain systems that mediate the perception of threat in the environment.
The possible effects of histamine (HA) locally applied into the preoptic area (POA) on hippocampus-mediated behaviors were studied in adult male rats. Animals were double-implanted unilaterally with microinjection cannulae into POA and hippocampus (HPC). In experiment 1, HA was injected into POA and pyrilamine (H1-HA antagonist) or ranitidine (H2-HA antagonist) were microinjected into the ipsilateral HPC in two different doses. In Experiment 2, HA was injected into POA and the histamine antagonists were microinjected into the contralateral HPC. Ten min later the animals were tested in an automatic monitor activity. Horizontal, ambulatory and vertical movements were measured as general motor exploratory behaviors. Contact time (in seconds) to a circular metal rack positioned in the center of the animal activity monitor was also recorded as goal-directed exploratory activity. Results of Experiment 1 showed that HA in POA exerted an inhibitory influence on general motor behaviors and also on goal-directed activity. Ipsilateral administration of HA-antagonists into HPC blocked the HA effect on behavior. Results of Experiment 2 showed that the administration of the HA-antagonists in any of the two doses used were not able to block the depressive actions on behavior caused by HA into POA. In conclusion, data suggest that POA is linked to the ipsilateral HPC through histaminergic influence to control behavioral patterns induced by novelty.
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The parahippocampal cortex is ascribed a key function in mediating reciprocal connections between neocortical association areas and the hippocampal formation. Within this complex the lateral entorhinal cortex (LEC) seems to stand out as an important interface exerting modulating influence upon cognition and memory by way of its connections with the hippocampal formation and temporal cortex (TC), respectively. The purpose of the present study was to compare effects of TC/LEC disruptions in a novelty test with results previously obtained in the same test following lateral perforant path (LPP) disruptions. Further, effects of TC/LEC lesions on proactive memory were examined, since a profound impairment in retroactive memory has previously been found. Rats bearing TC/LEC lesions or LPP lesions behaved differently in the novelty test. It was also shown that the impairment in proactive memory was less severe than the one seen in retroactive memory following TC/LEC lesions. The results are discussed in terms of a highly integrative role of LEC.
9 rats received bilateral lesions to the anterodorsal caudate nuclei and 9 rats underwent sham operation procedures. After recovery the subjects were observed in an apparatus allowing access to familiar or novel stimuli. The caudotomized rats spent a significantly greater proportion of time exploring the novel stimuli. The results were not consistent with the suggestions that following damage to the caudate nucleus animals were unresponsive to novelty, however, they did support earlier findings implicating the caudate nucleus in learning and memory processes.
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Alcohol is reported to impair acquisition and learning processes and it is considered a depressant of the brain activities impairing rapidity and consistency of some behaviors. The experiments reported here are concerned with the exploratory performances of the already described subpopulations of Albino mice under the effect of alcohols of different types.