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PubMed1992

Neurological and behavioral outcomes of focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the neurobehavioral consequences of focal ischemia in rats. METHODS: We induced permanent occlusion of the left middle cerebral artery in 14 Sprague-Dawley rats, and used 13 sham-operated rats as controls. During surgery, brain temperature and body temperature were kept at normothermia. Neurobehavioral studies (neurological examination, passive avoidance task, Y maze test, and modified open-field test) were carried out 4 days after ischemia before killing the rats to evaluate histological damage. RESULTS: Ischemia induced large infarcts in the cortex (138.6 +/- 8.5 mm3) and caudate-putamen (48.8 +/- 2.6 mm3) and, compared with sham-operated rats, produced a dramatic neurological deficit (p less than 0.001) characterized by sensorimotor dysfunctions and hemiplegia. Memory retention was significantly (p less than 0.05) impaired in the passive avoidance task, but neither vigilance and exploratory behavior measured in the modified open-field test nor working memory evaluated in the Y maze test were disturbed. Infarct size was not correlated with the neurological or behavioral deficits. CONCLUSIONS: This lack of correlation indicates the necessity of carrying out parallel histological, neurological, and behavioral studies in any assays of new drugs using this model of focal ischemia.

Animals↗

PubMed1996

Expression in brain of amyloid precursor protein mutated in the alpha-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice.

A double mutation in the alpha-secretase site in the betaA4 region of mouse amyloid precursor protein (APP) reduced its secretion from COS cells, polarized MDCK cells and rat primary neurons. Expression of this mutant in the brain of mice, using the neuron-specific elements of the mouse Thy-1 gene promoter, resulted in transgenic mice that became progressively hyperactive, displayed seizures and died prematurely. In three different transgenic lines the severity of the phenotype was related directly to the expression levels of the transgene, estimated by both mRNA and protein levels. In addition, homozygous mice derived from each transgenic strain showed more severe symptoms which also occurred earlier in life than in heterozygotes. The observed symptoms were, however, not essentially different in the different lines. Increased aggressiveness, disturbed responses to kainic acid and N-methyl-D-aspartate, neophobia and deficiency in exploratory behavior were demonstrated in these mice. In the brain, the observed neuropathological changes included necrosis, apoptosis and astrogliosis in the hippocampus, cortex and other areas. The data demonstrate that incomplete or incorrect alpha-secretase processing of APP results in severe neurotoxicity and that this effect is expressed in a dominant manner.

Amyloid Precursor Protein Secretases↗

PubMed2000

Comparison of the effects of adrafinil, propentofylline, and nicergoline on behavior in aged dogs.

OBJECTIVE: To compare the efficacy of adrafinil, propentofylline, and nicergoline for enhancing behavior of aged dogs. ANIMALS: 36 Beagles between 9 and 16 years old. PROCEDURE: Dogs were randomly assigned to receive adrafinil (20 mg/kg of body weight, PO, q 24 h; n = 12), propentofylline (5 mg/kg, PO, q 12 h; 12), or nicergoline (0.5 mg/kg, PO, q 24 h; 12) for 33 days. Baseline behaviors in an open field and in kennels (home cage) were recorded before treatment. After treatment, behaviors in the open field were recorded 2 hours after drug administration on days 2, 15, and 28, and 10 hours after administration on days 7, 20, and 33. Behaviors in the home cage were recorded 2 and 7 hours after drug administration on days 4, 17, and 30. RESULTS: Treatment with adrafinil resulted in a significant increase in locomotion in each of the open-field tests and an increase in locomotion in the home cage. This latter increase was smaller and more variable than that in the open field. Locomotion was not affected by treatment with propentofylline or nicergoline. In the open field, sniffing decreased over time in all 3 groups, but the largest decline was observed in the propentofylline group. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with adrafinil may improve the quality of life of aged dogs by increasing exploratory behavior and alertness.

Adrenergic alpha-Antagonists↗

PubMed1985

Functional classification of different dopamine receptors.

A series of experiments is described in which behavioral models and intracerebral dialysis were used to study neurotransmitter release and which illustrate the functional properties of different dopamine receptors. Evidence is presented for the existence of postsynaptic D-1 dopamine receptors, which are preferentially stimulated by apomorphine and inhibited by SCH 23390, and postsynaptic D-2 receptors, which are preferentially stimulated by pergolide and inhibited by sulpiride. On the basis of results obtained following systemic and local treatment with picrotoxin it seems probable that D-2 receptors are located on GABA interneurons in the striatum. Furthermore, lesion studies indicate that the D-1 and D-2 receptors are related to different neuronal pathways. In contrast to postsynaptic dopamine receptors, presynaptic autoreceptors, as studied by recording the decrease in exploratory behavior and dopamine release, seem not to differ in their response to apomorphine and pergolide. Sulpiride selectively inhibits dopamine autoreceptors and is equally potent in inhibiting apomorphine and pergolide autoreceptor-dependent responses. In summary, the data strongly support the existence of functionally important D-1 and D-2 receptors.

Animals↗

PubMed1989

Hyperactivity induced by N-methyl-d-aspartate injections into nucleus accumbens: lack of evidence for mediation by dopaminergic neurons.

To test the hypothesis that the motor hyperactivity associated with intra-accumbens injections of N-methyl-d-aspartate (NMDA) results from stimulation (direct or indirect) of nucleus accumbens dopaminergic mechanisms, the behavioral effects of intra-accumbens and intraventricular NMDA were compared to those of the prototypic dopaminergic releasing agent, amphetamine, and the competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Drugs were injected into the right lateral ventricle, or bilaterally into the nucleus accumbens of rats. Locomotor activity was monitored electronically and by direct observation for 40 min prior to, and 1 hour after, drug treatment. Intra-accumbens injections of NMDA (0.4, 1.2 and 2.0 micrograms/side) produced dose-related increases in distance traveled, but had no significant effect on movement time or vertical movements. The NMDA-induced increase in distance traveled was temporally correlated with convulsive wild running, but not with exploratory behavior, suggesting that this increase may have been secondary to seizure-like activity. Intra-accumbens injections of amphetamine (10, 20 and 40 micrograms) or CPP (0.1 microgram) produced dose-related increases in all three measures. By the intraventricular route, the effects of NMDA were similar to those of intra-accumbens administration, whereas intraventricularly administered d-amphetamine had no effect. The behavioral effects of intra-accumbens NMDA cannot be explained by an NMDA receptor-mediated facilitation of dopaminergic neurotransmission; rather, this type of facilitation may be associated with competitive NMDA receptor antagonism.

Animals↗

PubMed2006

The medial amygdala controls the coital access of female rats: a possible involvement of emotional responsiveness.

Partner preference and paced mating tests were accomplished in ovariectomized female rats following bilateral radiofrequency lesions in the medial amygdala. Open field behavior and passive avoidance learning were also examined to investigate the underlying behavioral mechanism. Partner preference was determined in a chamber located between castrated and sexually active males. Airborne olfactory cues were presented to the female through small holes on the partition. The lesion diminished preference for the odor of sexually active males over that of castrated males, even after injection with a high-dose of estrogen. On the other hand, in a paced mating test the lesioned females without estrogen treatment showed a significantly shorter latency for entering the male's compartment in a two-compartment apparatus, which allowed the females, but not the males, to cross the barrier through a narrow opening at the bottom. However, an administration of estrogen and progesterone reduced the effect. The lesion had no effect on emotionality or exploratory behavior in an open field test, but it impaired passive avoidance learning capability. We suggest that a male poses an inherent threat to a female. The seemingly incompatible results of partner preference and paced mating tests can be compromised if the male is inherently aversive to the female; this emotional response can be removed by the medial amygdala lesion.

Amygdala↗

PubMed2006

Injections of urocortin 1 into the basolateral amygdala induce anxiety-like behavior and c-Fos expression in brainstem serotonergic neurons.

The amygdala plays a key role in emotional processing and anxiety-related physiological and behavioral responses. Previous studies have shown that injections of the anxiety-related neuropeptide corticotropin-releasing factor or the related neuropeptide urocortin 1 into the region of the basolateral amygdaloid nucleus induce anxiety-like behavior in several behavioral paradigms. Brainstem serotonergic systems in the dorsal raphe nucleus and median raphe nucleus may be part of a distributed neural system that, together with the basolateral amygdala, regulates acute and chronic anxiety states. We therefore investigated the effect of an acute bilateral injection of urocortin 1 into the basolateral amygdala on behavior in the social interaction test and on c-Fos expression within serotonergic neurons in the dorsal raphe nucleus and median raphe nucleus. Male rats were implanted with bilateral cannulae directed at the region of the basolateral amygdala; 72 h after surgery, rats were injected with urocortin 1 (50 fmol/100 nl) or vehicle (100 nl of 1% bovine serum albumin in distilled water). Thirty minutes after injection, a subgroup of rats from each experimental group was exposed to the social interaction test; remaining animals were left in the home cage. Two hours after injection rats were perfused with paraformaldehyde and brains were removed and processed for immunohistochemistry. Acute injection of urocortin 1 had anxiogenic effects in the social interaction test, reducing total interaction time without affecting locomotor activity or exploratory behavior. These behavioral effects were associated with increases in c-Fos expression within brainstem serotonergic neurons. In home cage rats and rats exposed to the social interaction test, urocortin 1 treatment increased the number of c-Fos-immunoreactive serotonergic neurons within subdivisions of both the dorsal raphe nucleus and median raphe nucleus. These results are consistent with the hypothesis that the basolateral amygdala and serotonergic neurons within the midbrain raphe complex are part of an integrated neural system modulating anxiety state.

Amygdala↗

PubMed1983

Rooting and the development of male sexual behavior in two inbred mouse strains.

The sexual development of C57BL 6/J and SEC/IReJ male mice was studied during twice-weekly pairings with estrus females from 5 weeks of age. SEC were far slower to begin copulating than C57 and their responses to the female included a much higher frequency of rooting. Rooting, where the male's snout is pushed below the female's flank and jerked upwards, declines over tests as the full copulatory pattern develops. SEC also spent a higher proportion of their time in close contact with the female and groomed her more than C57. Both strains showed more rapid development of copulation if testing was delayed until 10 weeks of age, especially if they had exposure to female scent during this maturation period. The frequency of rooting and the speed of development are inversely related in these strains, but in segregating hybrid populations no such relationship is maintained. It is argued that the slowness of SEC's development cannot be ascribed to low sexual motivation. The significance of rooting remains obscure, but it seems possible that it may represent an aspect of exploratory behavior that is highly developed in SEC and some other strains.

Animals↗

PubMedDate not supplied

Some central effects of brofaromine given repeatedly are phase-dependent.

Effects of the MAO-A-inhibitor brofaromine (BRO), 10 mg/kg po after repeated (twice daily for 14 days) administration on the spontaneous behavior (exploratory and basal locomotor activities) and the exploratory activity modified by methoxamine, clonidine and d-amphetamine in male Wistar rats were studied in both light and dark phases of a diurnal cycle (L: 0700-1900 h). After single administration BRO in the light phase had no effects. In the dark phase BRO decreased the exploration (62% of control, p less than 0.01), increased the clonidine-evoked hypoactivity and amphetamine-evoked hyperactivity. The L-D differences occurred also after repeated administration. BRO in the light phase did not influence the exploration, decreased basal locomotor activity, did not change methoxamine and clonidine action and potentiated the action of amphetamine. In the dark phase, however, it did not influence the exploration and basal locomotor activity, intensified the methoxamine effect, and did not change the clonidine and amphetamine actions. The results demonstrate that the effects of BRO on behavior in rats: 1) differ from the effects caused by other antidepressants which are not MAO inhibitors; 2) are phase-dependent after both single and repeated administration.

Amphetamine↗

PubMed2006

Toxicity and behavioral effects of dimethylsulfoxide in planaria.

In this work, we describe aspects of the toxicity and behavioral effects of dimethylsulfoxide (DMSO) in planaria. Planarian worms have traditionally been a favored animal model in developmental biology. More recently, this organism is being recognized as an animal model in neuropharmacology research. DMSO is often used in cell and tissue culture as a cryoprotectant agent and is also commonly used to enhance the solubility of hydrophobic drugs in aqueous solutions. This compound can elicit various physiological effects in both vertebrates and invertebrates. Many drugs and drug candidates are hydrophobic, needing solvents like DMSO to be able to reach their physiological targets. As planaria becomes increasingly popular in neuropharmacology research, a description of the DMSO effects in this organism is essential. We found that DMSO is toxic to planarians at concentrations above 5% (705 mM), with an LD(50) of 10% (1.4M) at exposure times above 5 min. At sub-toxic concentrations, DMSO decreases planarian exploratory behavior in a concentration-dependent manner. This reduction in locomotor behavior is reversible and preincubation-independent. DMSO at a concentration of 0.1% (14.1 mM), which is usually enough to solubilize hydrophobic substances in aqueous solutions, did not display any toxic or behavioral effects in planaria. Therefore, in this animal model, DMSO concentrations above 0.1% should be avoided in order to be able to reliably observe any behavioral or toxic effects of hydrophobic drugs.

Animals↗

PubMed1994

The ACTH(4-9) analog Org2766 modulates the behavioral changes induced by NMDA and the NMDA receptor antagonist AP5.

In studies on aged and brain-lesioned rats the chronic administration of the ACTH(4-9) analog Org2766 has been demonstrated to improve the behavioral performance. Those results suggest that maintenance of hippocampal functioning in senescence and facilitation of functional recovery after brain damage are not due to facilitated reinnervation of denervated structures as suggested in previous studies concerning regeneration of the PNS. Alternative explanations may refer to either the neuroprotective properties of the peptide as demonstrated when chronic treatment immediately follows the damage, or a peptide-induced general change in attention that indirectly may contribute to functional recovery. The behavioral effects after acute treatment with ACTH-like peptides have been previously associated with sustained attention by enhanced neuronal excitability of limbic structures. Now, a hypothesis accounting for both neuroprotection and enhanced attention is forwarded by supposing that the peptide exerts its influence by modulation of NMDA receptor activation. Therefore, the acute effects and interactions between the peptide and the NMDA receptor antagonist AP5 (D,L-2-amino-5-phosphonopentanoic acid), and the peptide and NMDA were studied in a water maze and an open field. Impaired water maze performance induced by an acute intracerebroventricular administration of AP5 was counteracted by the ACTH(4-9) analog Org2766, whereas the peptide alone did not affect spatial orientation. NMDA induced extreme locomotor activity at the periphery of the open field. Interestingly, the ACTH(4-9) analog strongly suppressed NMDA-induced enhanced locomotor activity and normalized the pattern of exploratory behavior.

2-Amino-5-phosphonovalerate↗

PubMed2004

Chronic prenatal exposure to carbamazepine and behavior effects on mice offspring.

OBJECTIVE: The purpose of this study was to assess the impact of chronic prenatal exposure to a therapeutic dose of carbamazepine on the behavior of mice offspring in a randomized, placebo-controlled manner. STUDY DESIGN: Twenty-eight C3H/He mice were assigned randomly to treatment groups that were given food that contained either carbamazepine (25 mg in 10 g food) or a placebo for 1 week before mating and throughout gestation. Adult offspring from eight litters of each group were evaluated for standard tasks for motor, arousal/motivation, anxiety, and cognition. Statistical comparisons included analysis of variance and the Fisher exact test. RESULTS: Compared with the placebo group, there were no significant differences among the carbamazepine offspring in the duration of gestation, litter size, and birth weights. Fewer locomotor chamber movements were recorded in the carbamazepine group than in the placebo-exposed group at postnatal day 21 (469 vs 555 counts for 60 minutes, P<.03) and as adults (510 vs 688 counts for 60 minutes, P<.03) Coordination, balance, and exploratory behavior did not differ between exposure groups. A startle response from auditory arousal was decreased in carbamazepine-exposed adults (1.4% vs 21.9%, P<.03). Performances on anxiety/motivation tasks and on learning/memory tasks revealed no significant differences between exposure groups. CONCLUSION: Although prenatal exposure induced subtle arousal effects and slower locomotor activity, carbamazepine did not have an impact on coordination, cognition, or responses to anxiety-provoking conditions. Correlation in humans is recommended.

Animals↗

PubMed2001

Differential behavioral responses to cocaine are associated with dynamics of mesolimbic dopamine proteins in Lewis and Fischer 344 rats.

Differential behavioral and biochemical responses to drugs of abuse may reflect genetic makeup as suggested by studies of inbred Lewis (LEW) and Fischer 344 (F344) rats. We investigated locomotor activity, stereotypy signs, and levels of specific proteins in the nucleus accumbens (NAc) and ventral tegmental area (VTA) in these strains at baseline and following chronic administration of cocaine (30 mg/kg/day for 14 days). Using Western blot analysis, we replicated our previous findings of baseline strain differences and found lower levels of DeltaFosB immunoreactivity in NAc of F344 vs. LEW rats. F344 rats showed greater baseline locomotor activity, sniffing, and grooming compared to LEW rats. Chronic cocaine increased DeltaFosB levels in NAc in both strains, whereas adaptations in other proteins were induced in F344 rats only. These included reduced levels of tyrosine hydroxylase (TH) in NAc and increased TH and glial fibrillary acidic protein (GFAP) immunoreactivity in VTA. Chronic cocaine led to greater increases in overall stereotypy in F344 vs. LEW rats and decreased exploratory behaviors in LEW rats. Opposing effects by strain were seen in locomotor activity. Whereas F344 rats showed higher initial activity levels that decreased with cocaine exposure (tolerance), LEW rats showed increased activity over days (sensitization) with no strain differences seen at 14 days. Further, conditioned locomotor activation to vehicle injections was greater in F344 vs. LEW rats. These results suggest that behavioral responsiveness to chronic cocaine exposure may reflect dynamics of mesolimbic dopamine protein levels and demonstrate the role of genetic background in responsiveness to cocaine.

Animals↗

PubMed1994

N-0923, a selective dopamine D2 receptor agonist, is efficacious in rat and monkey models of Parkinson's disease.

Certain aminotetralins are known to be potent dopamine D2 receptor agonists. N-0923, [-]2-(N-propyl-N-2-thienylethylamino)-5- hydroxytetralin HCl, recognizes the high and low affinity states of the D2 receptor in membranes from bovine caudate with a Klow of 79 nM. The selectivity ratio is D2/D1 = 15 and D2/alpha 2 = 1.4. N-0923 also inhibits dopamine uptake and prolactin secretion, and it is an antagonist at the alpha 2 receptor. N-0923 (3-300 nmol/kg, s.c.) induced dose-dependent contralateral turning behavior in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. The ED50 of 30 nmol/kg was effective for 1 h. The positive enantiomer (N-0924; 300 nmol/kg, s.c.) was without effect. A hemiparkinsonian syndrome was induced in four Macaca nemestrina monkeys by unilateral infusion of the neurotoxin MPTP into the right carotid artery. Video recordings of free-moving behavior revealed bradykinesia, disuse of the contralateral upper limb and turning in a direction ipsilateral to the lesion. N-0923 (3-300 nmol/kg, i.m.) induced contralateral turning behavior, exploratory activity, and contralateral limb usage. The ED50 for turning (30 nmol/kg) was effective for 0.5 h. The potency order for induction of contralateral rotations was (+)-PHNO > N-0923 > bromocriptine. N-0924 (300 nmol/kg, i.m.) was ineffective. We conclude that N-0923 may be useful as a therapeutic agent in the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1990

Target recognition by the archenteron during sea urchin gastrulation.

During sea urchin gastrulation filopodia are sent out by secondary mesenchyme cells (SMCs) at the tip of the archenteron in continual cycles of extension, attachment, and retraction. Eventually the archenteron ceases its elongation and its tip localizes to the animal pole region of the embryo (Gustafson and Kinnander, 1956, Exp. Cell Res. 11, 36-57; Dan and Okazaki, 1956, Biol. Bull. 110, 29-42). We have investigated the mechanisms and specificity of this localization by analyzing filopodial behavior and by experimental manipulation of the interaction of the archenteron with the animal pole region. When the tip of the archenteron nears the animal pole, some filopodia make contact with a well-defined locus within this region. Filopodia that make contact with the locus remain attached 20-50 times longer than attachments observed at any other site along the blastocoel wall. The SMCs bearing the long-lived filopodia eventually change their phenotype by flattening and spreading onto this region. Several lines of experimental evidence indicate that contact with the animal pole locus, or "target" region, is crucial for the change in phenotype of the SMCs: (1) the phenotypic change can be induced precociously by bringing the animal pole region within reach of the tip of the archenteron early in gastrulation. Precocious contact with other regions of the blastocoel wall does not induce a similar change. (2) The phenotypic change can be delayed by placing the animal pole out of reach late in gastrulation, resulting in artificial prolongation of exploratory behavior by filopodia. (3) Ectopic combinations of animal pole ectoderm and archenterons in fused multiple embryos and chimaeras result in attachment of archenterons to the nearest available target, and (4) freely migrating SMCs are observed to migrate randomly within the blastocoel, then stop at the animal pole and undergo the change in phenotype. Filopodia rapidly attach to the animal pole when the shape of early gastrulae is altered such that the animal pole is less than 35 microns from the tip of the archenteron, even though such attachments only occur in normal embryos at the 2/3-3/4 gastrula stage. Since it has previously been shown that the archenteron elongates autonomously to 2/3 of its final length (Hardin, 1988, Development 103, 317-324), it appears that autonomous extension of the archenteron is required to place filopodia close enough to the animal pole to allow them to interact with it.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Paternal exposure of rabbits to lead: behavioral deficits in offspring.

Paternal exposures to exogenous agents have been reported to produce a variety of developmental defects in the offspring. In experimental animals, these effects include decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. The majority of experimental studies assessing nervous system function of offspring following paternal exposures have utilized rats as the experimental animal, but other species can be used. The National Toxicology Program (NTP) has initiated studies to validate the rabbit as an animal model for human reproductive toxicity, because rabbits are the smallest laboratory animal from which ejaculates can be collected repeatedly. An important part of reproductive toxicology is assessment of the reproductive ability of males following exposure, as well as developmental and functional assessment of their offspring. This article describes a pilot study and a main study to investigate the feasibility of using rabbits to assess the functional effects of paternal exposure to lead. The pilot study included seven male rabbits per group exposed for 15 weeks to lead acetate sufficient to produce 0, 50, or 110 micrograms/dl blood lead. The main study included 15 male rabbits per group exposed for 15 weeks to lead acetate to produce 0, 20, 40, and 80 micrograms/dl blood lead. At the conclusion of the exposure, male rabbits were mated with unexposed females. These females carried their litters to term, delivered, and reared their own offspring. The offspring were weighed at 5, 10, 15, 20, 25, 30, and some at 35 days of age. They were also tested for exploratory activity in a standard figure-eight "maze" for 30 min/day on days 15, 20, 25, and 30. A second assessment of exploratory behavior, along with a simple test of aversive conditioning, was attempted in the pilot study, but was judged not to be suitable for the main study. Of the 21 male rabbits that were mated in the pilot study, 16 produced viable litters (6/7, 6/7, and 4/7 in control, low- and high-lead groups, respectively), with a mean number of 6 live births/litter in each treatment group (range 2-8). Of the 60 rabbits mated in the main study, 57 produced litters, and two rabbits died giving birth. Significant postnatal deaths were observed in all groups, with about one half of the offspring dying before testing was initiated at day 15. There were no treatment-related effects on offspring weight gain through wearing. The data suggest that paternal lead exposure of rabbits may reduce figure-eight activity on day 25, the time of peak activity in the offspring.

Analysis of Variance↗

PubMed1996

5-HT(1A) receptors play an important role in modulation of behavior of rats in a two-compartment black and white box.

The involvement of serotonergic receptor subtypes in modulation of rat behavior in a black and white test box was studied. The high efficacy 5-HT(1A) receptor agonist 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetraline] was inactive, and the partial agonist buspirone showed an anxiolytic-like response that was weaker than the response to diazepam. The non-selective 5-HT(1) receptor agonists TFMPP [1-(trifluoromethylphenyl) piperazine] and eltoprazine were inactive. Low doses of the 5-HT(1A) receptor antagonist WAY 100.635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide] induced an anxiolytic-like response; 10-100 times higher doses induced an anxiogenic-like response. The 5-HT(2A/2C) and 5-HT(3) receptor antagonists ritanserin and ondansetron induced anxiolytic-like responses. The 5-HT(2A/2C) receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and the 5-HT(2A) receptor antagonist-MDL 100.151 [(=) chi-(2,3-dimethoxyphenyl)-1-[2-(4-fluorphenyl)ethyl]-4-piperidin-methanol] were inactive. 8-OH-DPAT potentiated the anxiolytic-like effect of ritanserin. It is suggested that 5-HT(1A) and 5-HT(2C) receptors are involved in mediation of exploratory behavior in rats, and that the 5-HT receptor subtype mediated effects may modulate one another.

Journal Article↗

PubMed2004

The effects of heavy particle irradiation on exploration and response to environmental change.

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.

Aging↗