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Biomedical subjects

K L Huhman

Publications and source records attributed to K L Huhman.

17 recordsLinked to original sources
PubMed1997

Tetrodotoxin blocks NPY-induced but not muscimol-induced phase advances of wheel-running activity in Syrian hamsters.

During the middle of the subjective day, circadian activity rhythms in Syrian hamsters can be phase advanced by a variety of stimuli including microinjection of neuropeptide Y (NPY) or muscimol into the suprachiasmatic nucleus (SCN). It is not known, however, if these treatments shift activity rhythms by acting directly on pacemaker cells within the SCN. In the present study NPY and muscimol were microinjected with either tetrodotoxin or saline in order to determine whether classical synaptic transmission within the SCN is necessary for the phase advances produced by NPY or muscimol. Blockade of sodium-dependent action potentials within the SCN prevented NPY- but not muscimol-induced phase advances. These data, along with our previous finding that bicuculline blocks NPY-induced phase advances, suggest that NPY requires sodium-dependent action potentials within GABAergic neurons in order to phase-shift the circadian pacemaker.

Action Potentials↗
PubMed1997

GABA(A) and GABA(B) agonists and antagonists alter the phase-shifting effects of light when microinjected into the suprachiasmatic region.

GABAergic drugs have profound effects on the regulation of circadian rhythms. The present study evaluated the effects of microinjections of GABAergic drugs into the suprachiasmatic region in hamsters on phase shifts induced by light and by microinjection of a cocktail containing vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) and gastrin-releasing peptide (GRP). The phase-advancing effects of light at circadian time (CT) 19 were significantly reduced by microinjection of GABA(A) or GABA(B) agonists into the SCN, but were not altered by microinjection of GABA(A) or GABA(B) antagonists. Microinjection of a GABA(B) agonist also reduced the phase-delaying effects of light at CT 13.5-14 while a GABA(B) antagonist increased the phase delays caused by light. Neither GABA(B) drug altered the phase delays produced by microinjection of a peptide cocktail containing VIP, PHI, GRP. These data indicate that changes in GABA(A) or GABA(B) activity within the SCN can alter the phase-shifting effects of light on circadian rhythms and support a role for GABA in gating photic input to the circadian clock.

Animals↗
PubMed1997

Serotonergic regulation of circadian rhythms in Syrian hamsters.

This study investigated the effects of (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthaline hydrobromide (8-OH-DPAT) on circadian rhythms in Syrian hamsters. Systemic administration of 8-OH-DPAT (0.75 mg in 150 microl saline) at circadian time 7 produced phase advances in the circadian activity rhythm. These 8-OH-DPAT-induced phase advances were blocked by microinjection of bicuculline (166 ng, 200 nl) into the suprachiasmatic nucleus, suggesting that GABAergic activity in the suprachiasmatic nucleus mediates the phase shifts produced by systemic injections of 8-OH-DPAT. Microinjection of 8-OH-DPAT (1 microg, 200 nl) or serotonin (0.7 microg, 200 nl) directly into the suprachiasmatic nucleus did not induce phase shifts at circadian time 7, suggesting that the phase shifting effects of systemic injection of 8-OH-DPAT are mediated outside the suprachiasmatic nucleus. To examine possible sites of action of 8-OH-DPAT, 8-OH-DPAT (0.5 microg (100 nl) or 1.0 microg (200 nl)) was microinjected into the intergeniculate leaflet, dorsal raphe nuclei, and the median raphe nucleus at circadian time 7. Significant phase advances were observed after microinjection into the dorsal raphe and median raphe but not the intergeniculate leaflet. These results support the hypothesis that systemic injection of serotonergic agonists can alter circadian rhythms via action in the midbrain raphe nucleus, and that the phase shifts induced by microinjection of 8-OH-DPAT into the raphe nuclei are mediated by a neurotransmitter other than serotonin within the suprachiasmatic nucleus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Neuropeptide Y phase shifts circadian rhythms in vivo via a Y2 receptor.

Neuropeptide Y (NPY) injected into the suprachiasmatic region 6 h before the onset of locomotor activity produces phase advances in circadian rhythms. The present study investigated whether the phase advances produced by NPY in Syrian hamsters are mediated by a Y1- or Y2-like NPY receptor by comparing the phase advancing effects of the Y1 agonist, [Leu31, Pro34]NPY, and the Y2 agonist, NPY(3-36), following their injection into the suprachiasmatic region. Microinjection of the Y2 agonist produced phase advances that were significantly greater than those produced by the microinjection of the Y1 agonist. These data support the hypothesis that the phase advancing effects of NPY in the suprachiasmatic region are mediated by a Y2-like NPY receptor, similar to results found in vitro.

Animals↗
PubMed1996

Bicuculline increases and muscimol reduces the phase-delaying effects of light and VIP/PHI/GRP in the suprachiasmatic region.

The present study investigated the effects of gamma-amino butyric acid (GABA)A-active drugs on the ability of light or coadministration of vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and gastrin-releasing peptide (GRP) to phase delay hamster activity rhythms. Microinjection of the GABAA agonist, muscimol, significantly (p < .01) reduced the phase-delaying effect of light administered at circadian time (CT) 13.5. By contrast, microinjection of the GABAA antagonist, bicuculline, significantly (p < .01) increased the phase-delaying effect of light administered at CT 13.5. Microinjection of muscimol or bicuculline into the suprachiasmatic nucleus (SCN) produced little or no effect on circadian phase when no light pulses were provided. Coadministration of muscimol with VIP/PHI/GRP significantly (p < .01) reduced the phase-delaying effect of VIP/PHI/GRP, whereas administration of bicuculline with VIP/PHI/GRP significantly (p < .05) increased the phase-delaying effect of these peptides. These data indicate that changes in GABAA activity within the SCN can modulate the phase-delaying effects of light and VIP/PHI/GRP during the early portion of subjective night.

Animals↗
PubMed1996

Rhythms of glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus.

The purpose of the present study was to determine whether there is a rhythm in glutamic acid decarboxylase (GAD) message in the suprachiasmatic nucleus (SCN) of rats housed in a light:dark cycle. The mRNAs encoding two isoforms of GAD (i.e., GAD65 and GAD67) were examined using in situ hybridization histochemistry. Computerized image analysis of film autoradiographs revealed that GAD65 mRNA was significantly higher in the light than it was in the dark. GAD67 mRNA levels were lower overall and did not decrease significantly in the dark. Following emulsion autoradiography, silver grain counts over individual SCN cells indicated that GAD65 mRNA was highest in the dorsomedial hypothalamus during the light. These data suggest that GAD mRNA varies rhythmically in the SCN and that mRNA levels are regulated differently within SCN subdivisions during the light:dark cycle.

Animals↗
PubMed1995

Analysis of the phase shifting effects of gastrin releasing peptide when microinjected into the suprachiasmatic region.

The role of gastrin releasing peptide (GRP) in phase shifting circadian rhythms was investigated. Microinjection of GRP into the suprachiasmatic region (SCN) region produced only small changes in the phase of free-running circadian activity rhythms in hamsters housed in constant darkness. However, co-administration of GRP with vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) produced significantly larger phase delays than GRP alone. These data support the hypothesis that GRP interacts with VIP and PHI within the SCN to induce phase shifts of circadian rhythms.

Animals↗
PubMed1995

Bicuculline blocks neuropeptide Y-induced phase advances when microinjected in the suprachiasmatic nucleus of Syrian hamsters.

Microinjection of neuropeptide Y (NPY) into the suprachiasmatic nucleus of the hypothalamus (SCN) during the middle of the subjective day (i.e. circadian time 6) causes large phase advances in circadian rhythms. The present study demonstrates that microinjection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline, completely blocks NPY-induced phase advances. These data indicate that GABAA activity within the SCN may mediate the phase shifting effects of some stimuli on the circadian pacemaker.

Animals↗
PubMed1995

Stressors, including social conflict, decrease plasma prolactin in male golden hamsters.

Following exposure to a stressor, plasma prolactin (PRL) rises in most species. The purpose of the present study was to examine the effect of social conflict or of footshock stress on PRL responsiveness in male Syrian hamsters. Contrary to expectations, PRL was significantly lower in subordinate hamsters than in their dominant opponents or in controls following one, five, or nine exposures to social conflict. Similarly, PRL was reduced in hamsters subjected to a mild footshock stressor. By contrast, adrenocorticotropin, another stress-responsive hormone, was elevated following exposure to each of these stressors. We also demonstrate that PRL release is inhibited by dopamine as it is in other species by showing that there is a dose-dependent increase in PRL release following treatment with the dopamine receptor blocker, domperidone.

Adrenocorticotropic Hormone↗
PubMed1994

Vasopressin and sex differences in hamster flank marking.

Vasopressin (AVP) within the medial preoptic-anterior hypothalamic continuum (MPOA-AH) plays an essential role in the control of flank marking in Syrian hamsters. Sex differences are found in the scent marking of many mammalian species, including hamsters. The first two experiments tested the hypothesis that sex differences in flank marking are the result of sex differences in the availability of AVP for release in several CNS sites. No support for this hypothesis was provided because neither immunohistochemical analysis nor radioimmunoassay of tissue punches revealed sex differences in AVP immunoreactivity in the MPOA-AH or other sites likely to be involved in flank marking. The third experiment, which tested the hypothesis that sex differences in flank marking are the result of sex differences in the sensitivity or response of the MPOA-AH to AVP, found no sex differences in the amount of flank marking stimulated by microinjection of AVP in the MPOA-AH. These data provide no support for the hypothesis that sex differences in vasopressinergic activity are responsible for sex differences in flank marking.

Animals↗
PubMed1994

Neuropeptide Y microinjected into the suprachiasmatic region phase shifts circadian rhythms in constant darkness.

The geniculohypothalamic tract (GHT) is a projection from the intergeniculate leaflet to the suprachiasmatic nucleus (SCN). The GHT exhibits neuropeptide Y (NPY) immunoreactivity and appears to communicate photic information to the SCN. Microinjection of NPY into the SCN has been found to phase shift circadian rhythms of hamsters housed in constant light in a manner similar to the phase shifts produced by pulses of darkness or triazolam injections. In the present study, NPY was injected into the SCN of Syrian hamsters housed in constant darkness and was found to produce phase shifts similar to those seen in hamsters housed in constant light. Microinjections were not followed by wheel running during the subjective day (the time when NPY microinjections are followed by significant phase advances). These data suggest that NPY produces phase shifts by some mechanism other than by inducing wheel running or by inhibiting the response of SCN neurons to light and supports a role for NPY in nonphotic shifting of the circadian clock.

Animals↗
PubMed1992

Hormonal responses to fighting in hamsters: separation of physical and psychological causes.

Male Syrian hamsters were paired and allowed to interact with a conspecific for 15 min a day for 4 days. On the fifth day, the animals were again paired, but they were kept physically separated by a mesh partition that allowed visual, olfactory, and auditory contact between the animals. Controls were placed with conspecifics on each of the 5 testing days, but the partition between them was never removed. Hamsters that were submissive on days 1-4 exhibited elevated plasma adrenocorticotropin-like immunoreactivity (ACTH-LI), beta-endorphin-like immunoreactivity (B-EP-LI), and cortisol on day 5 even though no fighting occurred on that day. Dominant hamsters did not differ from controls. These data support the hypothesis that there is an important psychological component to the pituitary-adrenocortical response in defeated hamsters.

Adrenocorticotropic Hormone↗
PubMed1991

Acute and repeated exposure to social conflict in male golden hamsters: increases in plasma POMC-peptides and cortisol and decreases in plasma testosterone.

The purpose of the present study was to characterize the hormonal response of dominant and submissive male hamsters to acute and repeated exposure to social conflict. We found that submissive, but not dominant, males exhibited elevated plasma levels of adrenocorticotropin (ACTH), cortisol, and beta-endorphin (beta-EP) following one exposure to an agonistic encounter. After five exposures to a dominant opponent, submissive males showed smaller, but still significant, elevations in these plasma hormones. After nine exposures, submissive hamsters showed significant elevations only in plasma ACTH and beta-EP. Plasma testosterone was significantly suppressed in submissive males that fought nine times. We conclude that hamsters are a useful species with which to study the neuroendocrine correlates of social behavior.

Adrenocorticotropic Hormone↗
PubMed1991

Plasma cyclic AMP increases in hamsters following exposure to a graded footshock stressor.

To assess the utility of plasma cyclic AMP (cAMP) as a sensitive physiological index of an animal's arousal level, we exposed male hamsters to various intensities (0.0-2.0 mA) of a footshock stressor. The plasma cAMP response was directly related to stimulus intensity. Ratings of behavioral arousal were positively correlated with plasma cAMP values. We conclude that plasma cAMP may be a useful index of arousal.

Animals↗
PubMed1990

Effects of social conflict on POMC-derived peptides and glucocorticoids in male golden hamsters.

The effects of fighting and footshock on circulating adrenocorticotropin-like immunoreactivity (ACTH-LI), cortisol, corticosterone, beta-endorphin-like immunoreactivity (beta-EP-LI), and beta-lipotropin-like immunoreactivity (beta-LPH-LI) were examined. In the first experiment, catheterized males were paired with large, ovariectomized females for 15 min. Submissive males exhibited significant increases in plasma ACTH-LI, cortisol, corticosterone, and beta-EP-LI. In the second experiment, two males were paired to determine whether the hormonal response in submissive animals was different from that in dominant hamsters. The pattern and magnitude of the hormonal response was also compared to that following a commonly used stressor-footshock. Footshock was associated with large increases in each of the plasma hormones measured. Submission, but not dominance, was associated with smaller, but still significant, increases in ACTH-LI, cortisol, beta-EP-LI and beta-LPH-LI. The data indicate that fighting is not a generalized stressor. "Losing," in particular, appears to be an example of a biologically relevant stressor.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Estradiol increases the behavioral response to arginine vasopressin (AVP) in the medial preoptic-anterior hypothalamus.

Flank marking, a form of hamster scent marking controlled by arginine vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH), is altered by circulating levels of gonadal hormones. We hypothesized that gonadal hormones influence flank marking either by altering the availability of AVP for release in the MPOA-AH or by altering the sensitivity or responsiveness of MPOA-AH neurons to AVP. We examined the levels of AVP immunoreactivity (AVP-IR) over the estrous cycle in the MPOA-AH and other areas. Arginine vasopressin immunoreactivity did not vary in the areas examined as a function of the stage of the estrous cycle. In Experiment 2 we measured flank marking after MPOA-AH microinjection of AVP in ovariectomized hamsters receiving estradiol or empty Silastic capsules. Hamsters implanted with estradiol capsules marked significantly more in response to AVP than did hamsters receiving no hormone replacement. These results support the hypothesis that estradiol influences flank marking by altering the sensitivity or responsiveness of the MPOA-AH or its efferents to AVP. Additionally, we observed an unexpected effect of AVP in estradiol-treated hamsters. After microinjection with 90 microM AVP, lordosis occurred spontaneously in 60% of the hamsters even though no male was present. We suggest that female hamsters may be a useful model to further investigate the role of AVP and AVP-like peptides in female sexual behavior.

Animals↗