Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some experiments, reported in detail elsewhere, on the effects of mother-infant separation in rhesus monkeys are here reviewed and compared. They involved 4 groups--one in which mothers were removed for 13 days leaving the infant in the social group; one in which infants were removed; one in which mothers and infants were removed and separated; and one in which mothers and infants were removed but not separated. The nature of separation experience had a profound effect on the infant's response: infants left in a familiar environment while their mothers were removed showed marked but brief 'protest' and then profound 'despair', whilst infants removed to a strange cage showed more prolonged 'protest'. A major factor determining the effects of the separation experience in the weeks following reunion is the degree to which the mother-infant relationship has been disturbed by it. The multiplicity of factors affecting the outcome of a separation experience are discussed.
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PMID:Some factors influencing the effects of temporary mother-infant separation: some experiments with rhesus monkeys. 40 20

The present study examined the behavioral, neurochemical and endocrinological characteristics of aggressive, male alpha-mice. These mice inflict severe bite marks on other male mice in their cage, but are not attacked themselves. The characteristics of the alpha-mice were compared with those of submissive mice, and of control mice taken from cages in which no severe fighting was observed. The behavioral tests used were Porsolt's swim test of behavioral 'despair', a plusmaze test of anxiety, a holeboard test of exploration and locomotor activity, and a test of seizure threshold to bicuculline. The alpha-mice were found to be immobile in the swim test for a shorter time than the submissive and control mice, and the submissive mice for a longer time than the controls. In the holeboard, the alpha-mice spent less time making exploratory head-dips than the other mice. Submissive mice had elevated 5-HIAA levels in the hypothalamus, hippocampus and brainstem, and the alpha mice had reduced concentrations of dopamine in the brainstem. There were no significant differences in plasma corticosterone or testosterone concentrations between the groups. These findings indicate that in alpha-mice, a number of behavioral and neurochemical characteristics appear together with the unusually high aggressiveness towards cage-mates.
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PMID:Behavioral, hormonal and neurochemical characteristics of aggressive alpha-mice. 281 52

Effects of social stimuli on behavioral and physiological responses were examined in infant rhesus monkeys at 4 and 9 months of age. Infants and mothers were removed from the social group and housed as dyads. Following this period, infants were removed and separated under four counterbalanced conditions: (a) totally isolated--placed in a holding cage for 24 hr; (b) mother present, no contact--housed in a single cage in view of their mother, no contact; (c) mother present, contact--similar to above, with mother in proximity to the infant; and (d) peer present--separated but in proximity to a peer. In the first experiment, the infants rarely vocalized when totally isolated but showed high rates of vocalization in the presence of the mother, both with and without contact. In the mother-present conditions, they failed to show a plasma cortisol response. In contrast, totally isolated infants showed a significant elevation in plasma cortisol. At 9 months of age, these infants were separated for 3 days under two different conditions: mother present and totally isolated. Once again, the infants that were totally isolated showed little vocalization but significant elevations in plasma cortisol. In contrast, infants separated in the presence of their mothers showed high vocalization rates but no cortisol response. The concepts of protest and despair are discussed as they relate to behavioral and physiological differences observed following different separation paradigms.
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PMID:Behavioral and hormonal responses to separation in infant rhesus monkeys and mothers. 384 17

Three 27-month-old infant gorillas living with their mothers and a silverbacked male were separated to a cage for 24 weeks. The infants initially showed threat responses and increased locomotion, characteristic of the protest stage of anaclitic depression in children. Within several days, these were replaced by dorso-ventral contact among the infants as well as self-holding and fetal positioning. Additionally, social and solitary play and object examination occurred at lower levels through separation than in the pre-separation condition. These changes were characteristic of the despair stage of separation. There was a substantial recovery of many infant nonsocial and social behaviors in the later months of the separation. Upon reunion, the infants did not immediately engage in attachment behaviors with their mothers, and spent more time in contact with each other than with their mothers for the first several days, indicating detachment. Following this, there was an increase in mother-infant attachment behaviors.
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PMID:Separation and depression in infant gorillas. 784 98

The present study evaluated the effects of mixed opioid drugs on the severity of cocaine (COCA) toxicity by examining stress-related behavioral alterations in mice. In order to ascertain the strength of the stress, the continuous observation of the behavioral symptoms in the cage and the forced swimming test (Porsolt test) were performed in the COCA (75 mg/kg, i.p.)-treated groups, with or without the mixed mu-kappa receptor-related opioid drugs, buprenorphine (BUP) and pentazocine (PEN). Using the high-sensitivity activity measuring instrument Supermex, both the spontaneous behaviors in the cage and the forced swimming behaviors in the water were assessed as activity counts. The behavioral alterations in the COCA-treated groups were compared with a group of mice given a 10 min immobilization stress (IM group). In the COCA-only group, a prolonged increase in the spontaneous behaviors accompanied by convulsive seizures was observed even in the surviving mice, unlike in the IM group. However, an acceleration of behavioral despair in the Porsolt test similar to that observed in the IM group was observed in the COCA group after the disappearance of the acute toxic symptoms (5 hours after the COCA treatment). Among the opioid-treated groups, the mortality rate was attenuated only in the COCA-BUP (0.25 mg/kg, i.p.) group. In the COCA-BUP group, a prolonged suppression of the morbid hyperactivity in the cage except for the convulsive seizures, and a normalization of the swimming behavior in the Porsolt test were observed in the survivors. On the other hand, in the COCA-PEN (5 mg/kg, i.p.) group, the swimming behavior in the Porsolt test was abnormally increased in addition to the prolonged morbid hyperactivity in the cage. Therefore, the COCA-induced stress-related behaviors were normalized in the group of mice treated with BUP, a group with a good prognosis.
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PMID:Stress-related behavioral alterations accompanying cocaine toxicity: the effects of mixed opioid drugs. 1119 74

Previous animal stress studies have illustrated the marked impact of coping on subsequent behavior and physiology by using shock as the stressor. The current study evaluates the generality of shock stress controllability effects in a new swim stress paradigm on several dependent measures: behavioral despair, analgesia, shuttlebox escape, and alcohol reactivity. In this new paradigm, rats in the escape group are able to learn the behavioral response as evidenced by significant reduction in the acquisition of a lever press response. Both escape and yoked subjects showed "behavioral despair" in comparison to both restrained and home cage controls when tested 24 h later. In the standard shuttlebox escape task 24-h post-stress, no group differences emerged, although a trend for poorer performance in the yoked subjects was evident. No group differences were observed in pain sensitivity after the first or second forced swim exposure. Finally, stress controllability effects were observed in behavioral reactivity to alcohol 2-h post-stress as measured by rotarod performance. This effect is opposite to the previous observations with the tailshock stress controllability paradigm. These results suggest that (1) there are certain similarities, but some fundamental differences between the behavioral endpoints measured following intermittent swim stress in comparison to the well-established effects of the intermittent tailshock stress model and (2) the qualitative nature of a stressor may markedly influence the behavioral and physiological consequences of stress and coping.
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PMID:Behavioral analysis of stress controllability effects in a new swim stress paradigm. 1126 31

Nociceptin/orphanin FQ (N/OFQ) is a newly discovered neuropeptide that has been implicated in the neurobiological regulation of the behavioral responses to stress and fear. To investigate the role of this peptide in the expression of stress/anxiety-related behaviors in mice, a gene targeting approach to disrupt N/OFQ in the pre-proN/OFQ gene was used. The impact of environmental housing conditions (single and social housing) was assessed on N/OFQ-knockout male and female mice in different experimental paradigms known to trigger distinctive types of stress and anxiety states. Neurological examination of homozygous mutant adult animals indicated that basic neurological functions (vision, audition, olfaction, tactile and pain sensitivity, motor performances) were normal. When housed individually, N/OFQ-knockout animals displayed responses similar to control animals in behavioral tests of emotional reactivity (behavioral despair, locomotor activity, light-dark preference, and acoustic startle tests). In contrast, increased emotional responses were detected when individually housed mice were crowded together (five per cage) under conditions of competitive access to food, water, space, and social contacts. Under those conditions, male mice deficient for N/OFQ developed greater home-cage aggression and increased fear/anxiety-like behaviors in the light-dark and acoustic startle tests, when compared to their wild-type littermates. Group-housed female mutants also showed higher level of anxiety in the acoustic startle test, but needed additional restrain stress to express detectable levels of anxiety in the light-dark test. These data indicate a clear environment-induced rise in fear reactions of N/OFQ-knockout mice. They further suggest that N/OFQ system is essential for development of adequate coping strategies to acute and chronic stress.
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PMID:Impact of environmental housing conditions on the emotional responses of mice deficient for nociceptin/orphanin FQ peptide precursor gene. 1294 1

KKHA-761, 1-{4-[3-(3,4-dimethoxy-phenyl)-isoxazol-5-yl]-butyl}-4-(2-methoxy-phenyl)-piperazine, has a high affinity (Ki=3.85 nM) for human dopamine D3 receptor with about 70-fold selectivity over the human dopamine D(2L) receptor (Ki=270 nM). KKHA-761 also showed high affinity for cloned human 5-HT1A receptor (Ki=6.4 nM). KKHA-761 exhibited D3 and 5-HT1A receptor antagonist activities in vitro, reversing dopamine- or 5-HT-mediated stimulation of [35S]GTPrS binding. The in vivo pharmacological profile of KKHA-761 was compared with both typical and atypical antipsychotics including clozapine and haloperidol. Apomorphine-induced dopaminergic behavior, cage climbing, in mice was potently blocked by a single administration (i.p.) of KKHA-761 (ID50=4.06 mg/kg) or clozapine (ID50=4.0 mg/kg). Cocaine- or MK-801-induced hyperactivity in animals was markedly inhibited by KKHA-761 or clozapine. In addition, KKHA-761 significantly reversed the disruption of prepulse inhibition (PPI) produced by apomorphine in mice, indicating the antidopaminergic or antipsychotic activity of KKHA-761 in mice. However, KKHA-761 was inactive in the forced swimming behavioral despair model in mice, suggesting lack of antidepressant properties. KKHA-761 attenuated the hypothermia induced by a selective dopamine D3 agonist, 7-OH-DPAT, in mice, whereas clozapine enhanced it. Moderate doses of both KKHA-761 and clozapine did not increase serum prolactin levels in rats. Lower doses of, however, haloperidol significantly increased prolactin secretion. KKHA-761 did not induce cataleptic response up to 20 mg/kg, but significant catalepsy was shown at lower doses of clozapine and haloperidol. Furthermore, KKHA-761 showed a low incidence of rotarod ataxia (TD50=34.4 mg/kg, i.p.) in mice. The present results, therefore, suggest that KKHA-761 is a potent antipsychotic agent with combined dopamine D3 and serotonin 5-HT1A receptors modulation activity, which may further enhance its therapeutic potential for anxiety, psychotic depression, and other related disorders.
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PMID:KKHA-761, a potent D3 receptor antagonist with high 5-HT1A receptor affinity, exhibits antipsychotic properties in animal models of schizophrenia. 1621 22

The present study was aimed to determine whether the urine from donor rats, which were physically stressed (UD-PS) by unavoidable electric footshocks, produces despair in receptor partner rats (RP) in the long-term. For each trial, an RP rat was placed during 10 min once per day for 21 days in a small non-movement-restricting cage impregnated with the urine collected from a UD-PS rat. Control rats, free of stimulation, maintained their locomotion and immobility scores at basal values throughout the 21-day test. After 21 days of stressing experience [F(2,90)=15.22, P<0.0001] locomotion significantly increased in RP rats (r=0.938, P<0.01), whereas in the UD-PS group locomotion decreased (r=-0.606, P<0.05). The RP and UD-PS groups displayed the longest time of immobility [F(2,90)=8.83, P<0.001] in the forced-swim test (RP, r=0.886, P<0.05; UD-PS, r=0.962, P<0.001) compared with the control group (r=-0.307, NS). We conclude that the RP became similarly despaired as the UD-PS group through the action of 2-heptanone, a ketonic compound identified in UD-PS urine by HS-GC/MS techniques. This ketone was found to be increased [F(2,15)=3.50, P<0.05] from the 1st day of unavoidable electric footshocks, and to induce despair, an effect reverted [F(2,21)=16.5, P<0.0001] by imipramine (5.0 mg/kg) in another group of rats.
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PMID:Urine from stressed rats increases immobility in receptor rats forced to swim: role of 2-heptanone. 1740 5

The extracellular signal-regulated kinase (ERK) pathway mediates neuronal plasticity in the CNS. The mood stabilizers lithium and valproate activate the ERK pathway in prefrontal cortex and hippocampus and potentiate ERK pathway-mediated neurite growth, neuronal survival and hippocampal neurogenesis. Here, we examined the role of the ERK pathway in behavioral plasticity related to facets of bipolar disorder. Mice with ERK1 ablation acquired reduced phosphorylation of RSK1, an ERK substrate, in prefrontal cortex and striatum, but not in hippocampus or cerebellum, indicating the ablation-induced brain region-specific ERK signaling deficits. ERK1 ablation produced a behavioral excitement profile similar to that induced by psychostimulants. The profile is characterized by hyperactivity, enhanced goal-directed activity and increased pleasure-related activity with potential harmful consequence. ERK1-ablated mice were hyperactive in multiple tests and resistant to behavioral despair in the forced swim test. These mice displayed more home-cage voluntary wheel running activities, rearings in a large arena and open-arm visits in an elevated plus maze. Treatments with valproate and olanzapine, but not lithium reduced baseline activities in ERK1-ablated mice. All three treatments attenuated amphetamine-induced hyperactivity in ablated mice. These data indicate a profound involvement of ERK1 signaling in behavioral excitement and in the behavioral action of antimanic agents. The extent to which ERK pathway perturbation contributes to the susceptibility, mood switch mechanism(s) and symptom pathophysiology of bipolar disorder requires further investigation. Whether there is a shared mechanism through which mood stabilizers produce their clinical actions on mood, thought and behavioral symptoms of mania also requires further investigation.
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PMID:The extracellular signal-regulated kinase pathway contributes to the control of behavioral excitement. 1822 38


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