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Influences of early thyroid hormone manipulations: delays in pup motor and exploratory behavior are evident in adult operant performance.

The effects of thyroid hormone depletion and enhancement on litter size, survival, body mass, ambulation, quadrant crossing, home orientation, day of eye opening, and free serum T3 and T4 levels were examined in Study 1. In Study 2, the effects of the timing of prenatal insult and the level of thyroid hormone depletion on litter size, survival, body mass, and free serum T3 and T4 levels were examined. Upon the completion of Study 1, randomly selected pups were maintained on ad-libitum water and food for 2 years, and performance was evaluated on fixed and variable ratio schedules, fixed and variable interval schedules, and probability and reversal learning tasks (Study 3). In Study 4, human subjects diagnosed with and treated for either congenital hypothyroidism or congenital hyperthyroidism were tested on the operant procedures used in Study 3, as well as on a series of simple reaction time, serial timing, and conjunctive and disjunctive search tasks. Dose-dependent decreases in survival and delays in the presentation of early motor and exploratory skills were observed following thyroid hormone depletion; dose-dependent accelerations in the presentation of early motor and exploratory skills were observed following thyroid hormone enhancement. Pups that had been prenatally exposed to propylthiouracil (PTU) 1-2 years after the return of thyroid hormones to baseline levels were significantly less accurate at timing on fixed and variable interval schedules, demonstrated an inability to allocate responding on probability tasks, and committed more errors during original learning (OL) and on each reversal problem. Similar deficits were observed in follow-up tests with humans diagnosed with congenital hypothyroidism, as were deficits in serial timing and visual searching. Collectively, the present results demonstrate that the pervasive and negative effects of prenatal thyroid deficiency on early behavior are also expressed during adult operant performance.

Analysis of Variance↗

CNS activity of the methanol extract of Mallotus peltatus (Geist) Muell Arg. leaf: an ethnomedicine of Onge.

The aim of the present study was to investigate several neuropharmacological effects of the methanol extract and different fractions of Mallotus peltatus (Geist) Muell Arg. var acuminatus (Euphorbiaceae) leaves in Wistar albino rats and Swiss albino mice. General behavior, exploratory behavior, muscle relaxant activity and phenobarbitone sodium-induced sleeping time were studied. The results revealed that the crude extract at 200-300 mg kg(-1) p.o. and its fractions A and B at 50 mg kg(-1) caused a significant reduction in spontaneous activity (general behavioral profile), remarkable decrease in exploratory behavioral pattern (Y-maze and head dip tests), a reduction in muscle relaxant activity (rotarod, 30 degrees inclined screen and traction tests), and also significantly potentiated phenobarbitone sodium-induced sleeping time. The phytochemical study of crude leaf extract revealed the presence of tannin, triterpenoid, flavonoid, sterol, alkaloid and reducing sugar. Further fractionation and purification yielded two major fractions A (ursolic acid) and B (beta-sitosterol) with some fatty acids as the major compounds. The psychopharmacological activity of the crude leaf extracts appeared to be either due to fraction A (50 mg kg(-1)) or a combination of fractions A and B (50 mg kg(-1)) along with some fatty acids present in the n-butanol part of methanol extract of M. peltatus leaf (MEMPL).

Analgesics↗

Neuropharmacological profile of Barleria lupulina Lindl. Extract in animal models.

Barleria lupulina Lindl. is a popular medicinal plant distributed in mountains of southern and western India. In the present work, the effect of methanolic extract of aerial parts of B. lupulina on CNS activity has been evaluated. The CNS activity was tested in several experimental models, in mice and rats: general behavior, exploratory behavior, muscle relaxant activity, conditioned avoidance response and phenobarbitone sodium-induced sleeping time tests. The aerial parts of the plant B. lupulina was extracted with methanol and the solvent was removed by vacuum distillation. The methanol extract (100, 200 and 300 mg/kg) showed reduction in general behavioral pattern (spontaneous activity, alertness, awareness, pain response and touch response) in a dose dependent manner. The extract was found to produce a significant reduction of the exploratory behavioral profile (Y-maze test, head dip test) and conditioned avoidance response with all the tested doses. The methanolic extract showed significant motor incoordination and muscle relaxant activity. The extract also potentiated phenobarbitone sodium induced sleeping time. Preliminary investigation showed that the methanol extract of B. lupulina has significant psychopharmacological activity.

Acanthaceae↗

N alpha-acetyl-[Arg8]vasopressin antagonizes the behavioral effect of [Cyt6]vasopressin-(5-9), but not of vasopressin.

It has been found recently that N alpha-acetyl-[Arg8]vasopressin (Ac-VP) is present in the brain of rats. The physiological significance of this peptide is as yet unknown. Therefore, the central nervous system effects of this peptide were investigated, namely, its effects on passive avoidance behavior, exploratory behavior and body temperature. The interaction of Ac-VP with the central nervous system effects of vasopressin (VP) was also studied. Ac-VP had a slight agonistic effect on passive avoidance behavior, i.e. it facilitated passive avoidance behavior at a dose 100 times higher than that of VP. Relatively low doses (3-10 ng) of Ac-VP attenuated passive avoidance behavior, which suggests that Ac-VP interfered with an endogenous compound involved in the control of passive avoidance responding. Ac-VP was also able, albeit in higher doses (30 ng), to competitively antagonize the effect of [Cyt6]VP-(5-9), a highly potent, putative endogenous metabolite of vasopressin in the rat brain. This antagonism could be due to an interaction of Ac-VP with sites other than the V1 vasopressin receptor. Ac-VP had no significant influence on other central nervous system effects of the hormonally active nonapeptide VP, such as exploratory behavior and body temperature. These effects were readily antagonized by the V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)VP. Ac-VP may be competitive antagonist of behaviorally active vasopressin metabolite(s) in the brain.

Animals↗

Effects of ACTH1-24 on male rat behavior in an exploratory, copulatory and socio-sexual approach test.

The effect of intraventricular application of ACTH1-24 on exploratory behavior, excessive grooming, and socio-sexual behavior in male rats was studied. It appeared that ACTH1-24 (1 microgram/animal) affects both excessive grooming and exploration. Sexual performance was delayed, as expressed in latency time to ejaculation, probably because of prolonged grooming behavior. The behavioral effects of ACTH are explained in terms of enhanced attention to external stimuli.

Adrenocorticotropic Hormone↗

Food neophobia, odor evaluation and exploratory sniffing behavior.

Past research has shown that people who avoid new foods (neophobics) and people who approach new foods (neophilics) differ in their sensory ratings of food and odor stimuli. The possible role of sampling behaviors in these differences was assessed in two studies. Participants completed neophobia surveys, then rated the pleasantness of odors while wearing a device that measured sniffing behavior. Neophobics rated the odors as less pleasant and sniffed them less vigorously in both studies. The results of these studies provide further evidence for differences in the way that neophobics and neophilics respond to novel, food-like stimuli. Neophobia influences willingness to try novel foods, expected liking for these foods, food-associated sampling behaviors and post-sampling ratings of food-like stimuli. It is proposed that the responses of neophobics and neophilics will differ when little information about the sensory properties of foods are available, and that these differences will moderate as sensory information is acquired.

Adolescent↗

Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors.

Blocking progesterone's metabolism to 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) with finasteride, a 5 alpha-reductase inhibitor, and effects on anxiolytic, exploratory, and antinociceptive behaviors of rats in behavioral estrus were examined. Rats in behavioral estrus received finasteride systemically (SC), to the hippocampus, or to control implant sites, the nucleus accumbens (NA) or ventral tegmental area (VTA), and were tested in horizontal crossing, open-field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive freezing tasks. Finasteride, SC or intrahippocampally, reduced 3 alpha,5 alpha-THP in the hippocampus relative to vehicle implants or finasteride to the NA or VTA. Systemic or intrahippocampal finasteride decreased central entries in the open field and open-arm time on the elevated plus-maze and increased freezing in response to shock relative to vehicle. Finasteride to the hippocampus decreased emergence latencies and increased social interaction, pawlick, and tailflick latencies relative to all other groups. Finasteride to the hippocampus of rats in behavioral estrous decreased anxiolysis and enhanced exploration and analgesia. In summary, these data demonstrate that decreases in anxiolytic behavior of behavioral estrous rats can be produced by reductions in 3 alpha,5 alpha-THP in the hippocampus, which suggest that elevations in 3 alpha,5 alpha-THP in the hippocampus may give rise to anxiolysis seen during behavioral estrus.

Animals↗

The effect of kindled seizures on the locomotory behavior of Long-Evans rats.

The incidence of attention deficit hyperactivity disorder (ADHD) is higher in children with epilepsy than in the general childhood population. The origin of the symptoms of ADHD seen in children with epilepsy is unknown. This experiment used an animal model to investigate whether seizures could be a cause of the hyperactivity sometimes associated with epilepsy. Sixteen male Long-Evans rats were implanted with electrodes, and 8 of them were kindled until generalized stage 5 seizures were elicited. Eight subjects were handled, but not kindled. The behavior of the rats in the two groups was compared in an open field test. The time spent in four behaviors was measured: exploratory behavior, immobility, eating, and grooming. Rats were tested after 5 stage 5 seizures, after 10 stage 5 seizures, after 15 stage 5 seizures, after a 2-week rest period, and after 5 more stage 5 seizures. Data were analyzed using the Mann-Whitney rank sum test. Twenty-four hours after a seizure, the kindled rats displayed a greater level of exploratory behavior than did the controls. They were not found to differ on any other measure. After a 2-week rest period, the group difference in behavior disappeared. When kindling was reinitiated, the kindled rats again showed increased exploratory behavior. The findings suggest that the increased exploratory behavior found in the kindled rats resulted from recent seizure activity. It may be that the hyperactivity seen in some children with epilepsy also results from recent seizure activity.

Animals↗

Protein and calorie malnutrition in infant cebus monkeys: growth and behavioral development during deprivation and rehabilitation.

The growth and development of 32 cebus monkeys were studied during a period of insult in nutritional or rearing conditions and after rehabilitation. Eight experimental groups of four animals each were subjected to one of four diets--control, protein restricted, calorie restricted, and protein-calorie restricted, and one of two rearing conditions-partial isolation or a comparatively enriched condition-in a 4 x 2 factorial design. The period of insult from 2 to 6 months of age was followed by 6 months of rehabilitation in both diet and rearing conditions. It was found that only diet affected physical growth, but both diet and rearing affected behavioral development and exploratory behavior. Whereas calorie deficiency produced a direct effect on behavior independent of rearing conditions, protein deficiency produced an effect only in combination with rearing restriction. The effect of protein-calorie deficiency had some characteristics in common with each of the other deficiencies. Retardation in rate of behavioral development was less severe than retardation in growth, most notably in the protein-restricted, enriched-rearing group, producing animals who were behaviorally mature for their size. All groups caught up in physical growth during rehabilitation but the protein-calorie restricted groups failed to recuperate completely in exploratory behavior.

Animals↗

Drug reward and intake in lines of mice selectively bred for divergent exploration of a hole board apparatus.

Individuals characterized as high-novelty seekers are more likely to abuse drugs than are low-novelty seekers, and it is possible that the biological substrates underlying novelty seeking and drug abuse are similar. We selectively bred replicate lines of mice from a B6D2 F3 hybrid stock for high exploratory behavior (HEB) or low exploratory behavior (LEB) as measured by the number of head dips on a hole board. To determine whether common genes might influence exploratory behavior and behaviors relevant to drug abuse, we tested HEB and LEB mice for conditioned place preference produced by ethanol and d-amphetamine and also examined oral methamphetamine intake. After four generations of selection, HEB and LEB mice did not differ in the magnitude of place preference for ethanol, but LEB mice showed a greater place preference for an amphetamine-paired location than did HEB mice. However, this difference did not replicate in mice tested from the fifth generation of selection. The selected lines also did not differ in sensitization to the locomotor stimulant effects of d-amphetamine that developed across the conditioning trials. Finally, HEB and LEB mice consumed equivalently low amounts of methamphetamine. These results suggest that common genes do not influence head dipping and several behaviors potentially relevant to drug abuse.

Administration, Oral↗

Specific behavioral effects related to age and cerebral ischemia in rats.

Rats at 4, 14, and 20 months of age were subjected to permanent occlusion of the left middle cerebral artery (MCAO) and the effects of age and ischemia assessed in tests for spatial learning (Morris' water maze), social behavior, olfactory learning, exploratory behavior, and motor function. Furthermore, the extent of ischemic damage to the brain of rats of 5 and 19 months of age was studied. An age-related decline in water-maze performance was observed, and aged rats were less agile, less explorative, and less frequently engaged in social interactions than young rats. After ischemia, mild memory impairment was observed in old rats, while changes in some exploratory behaviors were observed in young rats. Neuropathological analyses revealed a variable and limited degree of infarction in the piriform cortex and the insular cortex with no difference between age groups. In conclusion, the present study confirmed and extended current data on behavioral differences between young and old rats. MCAO had limited influence on the tested behaviors.

Aging↗

Response of extracellular zinc in the ventral hippocampus against novelty stress.

An extensive neuronal activity takes place in the hippocampus during exploratory behavior. However, the role of hippocampal zinc in exploratory behavior is poorly understood. To analyze the response of extracellular zinc in the hippocampus against novelty stress, rats were placed for 50 min in a novel environment once a day for 8 days. Extracellular glutamate in the hippocampus was increased during exploratory behavior on day 1, whereas extracellular zinc was decreased. The same phenomenon was observed during exploratory behavior on day 2 and extracellular zinc had returned to the basal level during exploratory behavior on day 8. To examine the significance of the decrease in extracellular zinc in exploratory activity, exploratory behavior was observed during perfusion with 1 mm CaEDTA, a membrane-impermeable zinc chelator. Locomotor activity in the novel environment was decreased by perfusion with CaEDTA. The decrease in extracellular zinc and the increase in extracellular glutamate in exploratory period were abolished by perfusion with CaEDTA. These results suggest that zinc uptake by hippocampal cells is linked to exploratory activity and is required for the activation of the glutamatergic neurotransmitter system. The zinc uptake may be involved in the response to painless psychological stress or in the cognitive processes.

Animals↗

Pre- or postsynaptic activity of 5-HT1A compounds in mice depends on the anxiety paradigm.

The purpose of the present study was to compare the contribution of pre and postsynaptic 5-HT1A receptors to the anxiolytic effects of serotonergic1A compounds in two animal models of anxiety. To this aim, the 5-HT1A ligands buspirone, ipsapirone, indorenate, and 8-OH-DPAT were tested in the burying behavior test and the avoidance exploratory behavior paradigm in control, pCPA-treated, and 5,7-DHT-lesioned mice, p-CPA and 5,7-DHT treatments did not modify the burying behavior per se, while 5-HT1A agonists produced a significant reduction in this behavior in both p-CPA- and 5,7,-DHT-lesioned animals. In the exploratory behavior paradigm, p-CPA per se but not 5,7-DHT increased the black/white transitions, interpreted as an antianxiety action. The ICV injection of 5,7-DHT blocked such effect of the 5-HT1A compounds in the avoidance exploratory behavior test. Data suggest that the effect of 5-HT1A compounds in the burying behavior test is mediated via the stimulation of postsynaptic receptors, while in the avoidance exploratory behavior paradigm these compounds act through the stimulation of the presynaptic site. Discussion is based on the differences between the animal models of anxiety.

8-Hydroxy-2-(di-n-propylamino)tetralin↗