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R Q Wan

Publications and source records attributed to R Q Wan.

12 recordsLinked to original sources
PubMed1998

Alteration of dopamine metabolites in CSF and behavioral impairments induced by neonatal hippocampal lesions.

Alterations of monoamine metabolites in CSF and behavioral abnormalities were studied in rats with neonatal hippocampal lesions and controls. Lesions of the ventral hippocampus were produced bilaterally by ibotenic acid on postnatal day 7. Lesion-induced neurochemical alterations and behavioral impairments were examined concurrently when rats were 12 weeks old. CSF from the cisterna magna was sampled repeatedly from freely moving rats. The levels of free 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were determined. An exposure to a novel environment induced hyperexploratory behavior and elevated the level of free DOPAC in CSF in lesioned rats. Although a swim stress increased the levels of free DOPAC and 5-HIAA in CSF in both control and lesioned groups, rats with hippocampal lesions had a further elevation of free DOPAC in CSF and greater spontaneous activity relative to controls shortly after stress. Amphetamine (1.5 mg/kg, i.p.) induced hyperlocomotion in lesioned rats compared to controls. For the control group, the levels of the three monoamine metabolites in CSF were not significantly influenced by amphetamine. However, for the lesioned group, the level of DOPAC significantly decreased compared to preinjection of amphetamine. The results indicate that neonatal hippocampal lesion-induced impairments can be manifested by behavioral and neurochemical abnormalities. Alterations of monoamine metabolites in CSF may be determined quantitatively and used as indices for monitoring lesion-impaired monoaminergic function in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Anticonvulsant effects of intra-hippocampal injection of TRH in amygdala kindled rats.

The anticonvulsant effects of intra-hippocampal thyrotropin-release hormone (TRH) were examined in amygdala kindled rats. Subjects were implanted unilaterally with an electrode in the amygdala and bilaterally with guide cannulae in the hippocampus, aimed at the dorsal and ventral dentate gyri. Rats were kindled daily with suprathreshold electrical stimulation (800 microA, 1 ms pulse width, 100 Hz, duration 0.5 s) until seizures were reliably elicited. The afterdischarge (AD) duration, seizure duration, and seizure stage were recorded daily, and AD thresholds were determined after kindling was completed. TRH was infused into each of the four cannulae of freely moving rats at doses of 0 (vehicle), 1.25, 2.5 and 5 microg/site. Five minutes after the last infusion, the rats received electrical stimulation at their AD threshold (mean = 135 microA) + 50 microA. TRH reduced the AD and seizure duration in a dose-dependent manner. At the dose of 2.5 microg/site, TRH also reduced AD and seizure duration in rats stimulated with suprathreshold current (800 microA). However, TRH had minimal effects on seizure stage irrespective of the stimulation intensity. These results suggest that the seizure-induced elevations of TRH in the hippocampus, as demonstrated in previous studies, may be part of an endogenous anticonvulsant compensatory mechanism and that further elevations of TRH in the hippocampus can produce anticonvulsant effects mainly by reducing the AD and seizure duration.

Amygdala↗
PubMed1997

Nonhippocampal muscarinic receptors are required for nonspatial working memory.

The effects of scopolamine on nonspatial working memory were examined in rats with hippocampal lesions and sham operations. Performance was examined using a continuous conditional discrimination task in an operant box. Choice accuracy measured nonspatial working memory. Response bias, delay interval responses, and response probability measured response preference, stimulus control, motivation, and sensorimotor ability. Scopolamine (0.05, 0.075, 0.1, and 0.15 mg/kg) or methylscopolamine (0.1 mg/kg) was injected (I.P.) 15 min prior to behavioral testing. In both control and hippocampal lesioned groups, choice accuracy declined as the delay interval increased. Scopolamine, but not methylscopolamine, produced a dose-dependent impairment of choice accuracy (interaction of Dose x Delay) in both groups. The scopolamine-induced impairment was not different between the control and hippocampally lesioned rats. Response bias, delay interval responses, and response probability were not affected by scopolamine except at the highest dose, which increased delay interval responses. The results suggest that central muscarinic receptors outside the hippocampus are important for working memory of nonspatial stimuli.

Animals↗
PubMed1997

Enhancement of postsynaptic sensitivity to dopaminergic agonists induced by neonatal hippocampal lesions.

The effects of neonatal hippocampal lesions on behavioral responsiveness to dopaminergic agonists and antagonists were examined. The ventral hippocampus was damaged bilaterally using ibotenic acid on postnatal day 7, and locomotor responses to dopaminergic agonists and antagonists were evaluated on postnatal day 35 (PD35), 56 (PD56), and 70 (PD70). Qunipirole (0.06, 0.125, 0.25, and 0.5 mg/kg SC), but not SKF38393 (5 and 10 mg/kg SC), increased locomotion in a dose-dependent manner in control and lesioned groups on PD35 and PD56. However, lesioned rats displayed a greater behavioral response to quinpirole than controls at the doses of 0.25 and 0.5 mg/kg on both PD35 and PD56. Amphetamine (1.5 mg/kg IP) increased locomotor activity in both groups on PD70, but this effect was greater in lesioned rats than in controls. Raclopride (0.25 and 0.5 mg/kg SC) and SCH23390 (0.01 and 0.02 mg/kg SC) blocked the amphetamine-induced hyperlocomotion in the lesioned and control groups. These results suggest that neonatal hippocampal lesion-induced behavioral hyperresponsiveness to amphetamine is likely related to an increased postsynaptic sensitivity of the D2 subtype of receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Neonatal hippocampal lesions induced hyperresponsiveness to amphetamine: behavioral and in vivo microdialysis studies.

The effect of neonatal hippocampal lesions on behavioral sensitivity to amphetamine (AMPH) and dopamine (DA) release in the nucleus accumbens (NAc) were examined. The ventral hippocampus was damaged bilaterally by ibotenic acid on postnatal day 7 (PD7). Spontaneous exploration and AMPH-stimulated locomotor activity were examined on postnatal day 35 (PD35) and day 56 (PD56). Extracellular DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were sampled using in vivo microdialysis while simultaneously AMPH-stimulated locomotion was examined in freely moving rats on PD56. Spontaneous exploration increased in rats with hippocampal lesions relative to controls on PD56 but not PD35. AMPH (0, 0.187, 0.375, 0.75, 1.5, and 3 mg/kg) enhanced locomotion dose-dependently in both control and lesioned groups. Locomotor activity was higher in lesioned rats than controls following AMPH at the dose of 0.75 mg/kg on PD35 and at the doses of 1.5 and 3.0 mg/kg on PD56. The basal level of DA in the NAc was not different between the hippocampal and control groups. AMPH (1.5 mg/kg) induced hyperlocomotion in lesioned rats relative to controls. DA release in the NAc for both groups was enhanced following injections of AMPH. However, neonatal hippocampal lesions had no further enhancement on AMPH-stimulated release of DA as compared to the control group. The levels of DOPAC and HVA in the NAc were altered by AMPH but not lesions. The level of 5-HIAA was not influenced by either lesions or AMPH. The results of neonatal lesion-induced hyperlocomotion suggest that an emergence of behavioral hyperresponsiveness to AMPH was dependent on an interaction of lesions, age of examination, and dose of the drug. A dissociation between the effect of AMPH on lesion-enhanced hyperlocomotion and a lack of a lesion-enhanced DA release in the NAc suggest that presynaptic release of DA had no major contribution to lesion-enhanced DA transmission in the mesolimbic DA system.

Aging↗
PubMed1996

Alterations of beta-endorphin-like immunoreactivity in CSF following behavioral training using a passive avoidance procedure.

The central opioid system may have an important influence on memory processes. In view of this, the concentration of beta-endorphin-like immunoreactivity (beta-ELIR) in cerebrospinal fluid (CSF) was measured by a radioimmunoassay in rats trained in a passive avoidance procedure. The beta-ELIR in CSF was examined immediately, 2, 5, 10, and 30 min after the learning trial in which rats were exposed to footshock (0, 0.25, or 1.0 mA for 3 s). Avoidance latency and beta-ELIR in CSF were examined 24 and 120 h after the learning trial. The beta-ELIR in CSF was increased at 5 min after the learning trial in rats exposed to footshock of 0.25 mA. The beta-ELIR in CSF was elevated at 5 and 10 min, followed by a significant decrease at 30 min after the learning trial in rats exposed to a footshock of 1.0 mA. Thus, although an increase in beta-ELIR in CSF was not, the duration of the increase was, related to the shock intensity. Interestingly, a decrease followed the increase in beta-ELIR in CSF which was significant only in rats exposed to the high shock intensity. Avoidance latencies were enhanced in a shock intensity-dependent manner at both 24 and 120 h retention tests. No change in beta-ELIR in CSF was found during retention trials. The results suggest that behavioral manipulations alter beta-ELIR in CSF. An increase in beta-ELIR in CSF may be highly associated with stressful and emotional responses during behavioral training.

Animals↗
PubMed1995

Opioid modulation of working memory: intraseptal, but not intraamygdaloid, infusions of beta-endorphin impair performance in spatial alternation.

The effect of beta-endorphin on spatial working memory was examined following microinfusions of beta-endorphin into the medial septal area and central amygdaloid nucleus in Long-Evans male rats. Working memory was assessed by spatial alternation in a T-maze. beta-Endorphin, 250 and 1000 ng/site, respectively, and muscimol, 20 ng/site, were infused into the medial septal area or central amygdaloid nucleus prior to behavioral testing. The hippocampal theta rhythm was examined following intraseptal infusions of beta-endorphin and muscimol. In the medial septal area, beta-endorphin and muscimol impaired choice accuracy and reduced the power of hippocampal theta rhythm. The degree of reduction in the power of hippocampal theta rhythm was correlated with the magnitude of behavioral impairment of choice accuracy in spatial alternation. In the central amygdaloid nucleus, beta-endorphin (1000 ng) and muscimol (20 ng) did not affect choice accuracy. The results suggest that septal, but not amygdaloid, opioid, and GABAergic activity modulate spatial working memory and hippocampal physiology.

Amygdala↗
PubMed1994

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: effects of delay and interference.

Parametric manipulations of the task demand were used to examine the role of the hippocampus and amygdala in nonspatial and spatial working memory in rats. Hippocampal lesions produced an immediate and long-lasting impairment of nonspatial working memory in an operant task. The memory deficits increased as the delay interval and the amount of proactive interference increased. Hippocampal lesions severely impaired spatial working memory in spatial alternation. Extensive postoperative testing reduced the magnitude of impairment of nonspatial but not spatial working memory. Amygdaloid lesions did not impair any aspect of performance in 2 tasks. The results suggest that the hippocampus, but not the amygdala, is involved in working memory and the task demand is a critical determinant for observing impairments of nonspatial working memory following hippocampal lesions.

Amygdala↗
PubMed1990

Changes in heart rate and body temperature during passive avoidance behavior in rats.

Heart rate, core temperature and gross locomotor activity during passive avoidance behavior in rats were recorded by a telemetry system connected to a computer data acquisition program. Passive avoidance latency and approach to the dark compartment were evaluated. Rats were assigned to five different groups, i.e., the shock groups that received different intensities of footshock (0.15, 0.25 and 1.0 mA, respectively, for 3 sec), a no footshock control group and a group that had no access to the dark compartment (i.e., no dark compartment control group). Retention tests were carried out 24 and 120 hr after the learning trial. Rats exposed to footshock showed a decrease in heart rate during the first 10 sec of the observation period in both retention tests. An average bradycardia was found in the lowest shock intensity group (0.15 mA) at both the 24- and 120-hr retention test whereas the other two groups (0.25 and 1.0 mA) showed a gradual increase in heart rate. This increase was more pronounced the longer the rats stayed on the platform. Similarly, a gradual rise in core temperature was observed in these rats as well as in the no dark compartment control group. The number of approaches to the dark compartment was significantly depressed in the group exposed to 1.0 mA footshock intensity. Gross locomotor activity was reduced in animals that exhibited maximum avoidance latency. Exposure of rats to the above-described behavioral paradigms induced autonomic activation resulting in changes in heart rate and temperature. These changes were not caused by gross locomotor activity and may thus be related to the various behavioral states.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

6-18F-L-dopa imaging of the dopamine neostriatal system in normal and clinically normal MPTP-treated rhesus monkeys.

Positron emission tomography following intravenous administration of 6-[18F]-L-fluorodopa was used to investigate the usefulness of PET for the assessment of normal and abnormal dopaminergic function. For this purpose, the incracerebral distribution of 6-[18F]-L-fluorodopa and its metabolites was evaluated in normal control and asymptomatic MPTP-treated rhesus monkeys. MPTP is a neurotoxic compound which destroys selectively the dapaminergic neurons of the nigrostriatal pathways in primates. The 18F accumulation was found to be significantly reduced in the striatum, putamen more than caudate, of the MPTP-treated animals compared to the normal controls. The 18F accumulation in dopamine-poor areas did not differ between the two groups. The ratios of striatum to dopamine-poor brain area were highly correlated to the concentrations of the dopamine metabolite, homovanillic acid, in the cerebrospinal fluid of the same animals. The findings are consistent with the hypothesis that "silent damage" to the dopaminergic nigral neurons may precede the onset of parkinsonism by many years and that PET scanner examination using 6-[18F]-L-fluorodopa may be useful in the detection of subtle dopaminergic dysfunctions as may exist in DA-related motor syndromes and neuropsychiatric disorders.

Animals↗
PubMedDate not supplied

D-cycloserine, a novel cognitive enhancer, improves spatial memory in aged rats.

D-cycloserine, a partial agonist of the NMDA receptor-associated glycine site, can enhance cognition. The present experiment examines the behavioral effects of D-cycloserine on cognitive deficits in male Fischer-344 rats, 24 months old. Rats 24 months old (n = 42) received either vehicle or one of 3 doses of D-cycloserine prior to testing. Young rats, 4 months old (n = 13), received vehicle prior to testing. Place discrimination and repeated acquisition were tested in the water maze and a variety of sensorimotor tasks were given. Aging impaired performance in all tasks. D-cycloserine improved performance in place discrimination and repeated acquisition. No doses affected sensorimotor function. These results support the hypothesis that D-cycloserine has cognition enhancing properties and that it may be useful in treating disorders involving cognitive impairment.

Aging↗