PubMed Health⌕ Search

Biomedical subjects

B Rusak

Publications and source records attributed to B Rusak.

At least 19 recordsLinked to original sources
PubMed2005

Circadian firing-rate rhythms and light responses of rat habenular nucleus neurons in vivo and in vitro.

The suprachiasmatic nuclei of the anterior hypothalamus serve as the principal pacemaker of the mammalian circadian system. Among its efferent targets are the habenular nucleus (Hb), especially the lateral Hb (LHb), which plays an important role in conveying input from the limbic forebrain to midbrain structures. We recorded extracellularly from single neurons in the LHb and medial Hb (MHb), both in vivo and using an in vitro slice preparation, to assess their responses to retinal illumination and the rhythmicity of their firing rates. Of cells recorded in the LHb, 42% were tonically activated or suppressed by retinal illumination, while significantly fewer cells recorded in the MHb responded to retinal illumination (19%). Of photically responsive cells, 68% in the LHb were activated and the remainder suppressed, while only 25% of those recorded in the MHb were activated. Cells in both the LHb and MHb showed higher baseline firing rates during the day than during the night in vivo, while photic responses were of significantly larger amplitude among LHb cells during the projected night than during the projected day. LHb cells recorded in vitro maintained their rhythmicity for two circadian cycles, but MHb cells did not show a rhythm in vitro. The habenula may play a role in linking circadian and motivational systems and may contribute to photic regulation of these systems, as well as to the rhythmicity of their function.

Action Potentials↗
PubMed2005

Circadian and light regulation of oxytocin and parvalbumin protein levels in the ciliated ependymal layer of the third ventricle in the C57 mouse.

The walls of the third ventricle have been proposed to serve as a bidirectional conduit for exchanges between the neural parenchyma and the cerebrospinal fluid. In immunohistochemical studies of mice, we observed that light exposure and circadian phase affected peptide staining surrounding the third ventricle at the level of the suprachiasmatic nuclei. Under high magnification, we observed robust staining for the neurohormone oxytocin and the calcium-binding protein parvalbumin associated with cilia extending into the third ventricle from the surrounding ventricular wall; no similar staining was observed for vasopressin or calbindin. Retinal illumination had opposite effects on levels of parvalbumin and oxytocin in the cilia: light exposure during late subjective night increased oxytocin staining, but decreased parvalbumin staining in the cilia. Preventing cellular transport with colchicine eliminated immunohistochemical staining for oxytocin in the cilia. There was also a significant daily rhythm of oxytocin immunostaining in the third ventricle wall, and in magnocellular neurons in the anterior hypothalamus. The results suggest that environmental lighting and circadian rhythms regulate levels of oxytocin in the cerebrospinal fluid, possibly by regulating movement of oxytocin through the third ventricle wall.

Animals↗
PubMed2002

Anatomical and temporal differences in the regulation of ZIF268 (NGFI-A) protein in the hamster and mouse suprachiasmatic nucleus.

Several immediate-early genes have been shown to be induced in the rodent circadian pacemaker, the suprachiasmatic nucleus, by retinal illumination at night. We compared spontaneous and light-evoked levels of the immediate-early gene protein ZIF268 (NGFI-A) in the Syrian hamster and C57BL/6J mouse suprachiasmatic nucleus. Exposure of both hamsters and mice to light pulses early and late in the subjective night caused increased ZIF268 immunoreactivity in the region of the suprachiasmatic nucleus that receives retinal innervation. In contrast to hamsters, mice also showed spontaneous increases in ZIF268 at both subjective night phases at the lateral edges of the suprachiasmatic nucleus. Light also evoked a significant increase in ZIF268 levels during the subjective day in the lateral suprachiasmatic nucleus, with few labeled cells in the ventral and dorsal suprachiasmatic nucleus. These results demonstrate a novel circadian pattern and regional differentiation of ZIF268 immunoreactivity in the suprachiasmatic nucleus of mice that differ from those in other rodents. There are pronounced species differences in both spontaneous and light-evoked expression of ZIF268 immunoreactivity.

Analysis of Variance↗
PubMed2001

Daily variation in the distribution of glycogen phosphorylase in the suprachiasmatic nucleus of Syrian hamsters.

Dynamic changes in astrocytic processes in the Syrian hamster suprachiasmatic nucleus (SCN) have been reported with maximal process extension in the light phase and maximal process retraction in the dark phase of a daily light:dark cycle. In the present study, we asked whether dynamic changes occur in the distribution of an astrocytic metabolic marker, glycogen phosphorylase (GP), using a histochemical assay to reveal the distribution of both active and total GP, in the hamster SCN. Changes in glial acidic fibrillary protein (GFAP) immunoreactivity also were assessed using a relative optical density measure (ROD). We observed changes in the localization and distribution of GP both in the SCN and in the paraventricular nucleus of the hypothalamus (PVN) as a function of time of day. In the light phase, there were concentrated, large, dot-like deposits of GP throughout the SCN and PVN on an empty background. In the dark phase, diffuse, small, granular particles were seen throughout both nuclei. Selectively, in the dark-phase SCN, these granular particles formed a rim of intense GP reactivity on the lateral, ventral, posterior, and medial borders. Significantly higher levels of GP reactivity were seen in anterior sections of the medial optic chiasm in the light phase. GFAP-immunoreactive astrocytic processes had higher ROD levels in the dark phase. In conclusion, the astrocytic metabolic marker, GP, exhibits a significant daily variation in localization in both the SCN and the PVN that correlates with dynamic changes in the distribution of astrocytic processes in the SCN. Increased GP activity also occurs in astrocytes among optic fibers subjacent to the SCN during light input.

Animals↗
PubMed2001

Phase-shifting effects of pituitary adenylate cyclase activating polypeptide on hamster wheel-running rhythms.

Pituitary adenylate cyclase activating polypeptide (PACAP38) is a putative neurochemical of the main retinal input to the mammalian circadian pacemaker housed in the suprachiasmatic nucleus (SCN). We assessed the phase-resetting effects of microinjection of PACAP38 into the SCN region on hamster wheel-running rhythms. When administered during the middle of the subjective day, PACAP38 evoked large but transient phase advances ( approximately 60 min), that were followed by small, steady-state phase delays. During the early subjective night, PACAP38 elicited small to moderate phase delays without any detectable concentration-dependence. Late in the subjective night, PACAP38 had no significant effects. Saline microinjection had no effect at any phase tested. These findings show that PACAP38 has small to moderate effects on the phase of the hamster SCN circadian pacemaker, including significant phase delays early in the subjective night.

Animals↗
PubMed2001

Sleep deprivation-induced c-fos and junB expression in the rat brain: effects of duration and timing.

Expression of the immediate-early genes (IEGs) c-fos and junB in the rat brain was studied in response to sleep deprivation (SD) starting at four time points during the light phase of a 12:12 light:dark cycle. Animals were confined to slowly rotating wheels for 3 or 6 h in order to prevent sleep. The numbers of c-Fos- and JunB-immunoreactive cells were assessed in seven brain regions previously reported to respond to SD with increased c-fos expression (medial preoptic area (MPA), cortex, anterior and posterior paraventricular thalamic nuclei, amygdala, caudate-putamen, and laterodorsal tegmental nucleus). While c-Fos was induced by SD in all regions studied, there were differences in levels of induction depending on the duration of deprivation and on the timing of the deprivation period during the light phase. The most robust induction occurred in most regions in response to 3-h deprivation periods beginning 3 h into the light phase. A similarly timed peak of induction was observed in the MPA and cortex after 6 h of SD. In two regions, the posterior paraventricular thalamic nucleus and amygdala, 6 h of deprivation induced greater c-Fos immunoreactivity than did 3 h of deprivation, collapsed across all phases tested. Increased JunB immunoreactivity in response to either duration of deprivation was more limited and was significant only in the MPA, cortex, caudate-putamen and amygdala. c-Fos and JunB immunoreactivity in the paraventricular hypothalamic nucleus was low and similar in control and deprived animals. These results indicate that both duration of prior wakefulness and time of day influence the extent of IEG expression differentially in brain regions responsive to SD. The results also suggest that the posterior paraventricular thalamic nucleus and amygdala might be primarily responsive to length of wakefulness (sleep drive), while the MPA and anterior paraventricular thalamic nucleus might integrate input related to both homeostatic sleep drive and circadian clock influences on sleep regulation.

Animals↗
PubMed2001

Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat.

The circadian pacemaker housed in the suprachiasmatic nucleus (SCN) synchronizes daily sleep-wake cycles, presumably by modulating the sleep-wake regulatory system, including ventrolateral preoptic area (VLPO) neurons. We used whole-cell patch-clamp recording to study the projections from the SCN to the VLPO in horizontal slices of rat hypothalamus. Single-pulse stimulation of the SCN region elicited postsynaptic currents (PSCs) in 20 of 66 neurons (30%) recorded within the VLPO region as verified by intracellular biocytin labelling. At a holding potential of -60 mV, the evoked PSCs had an amplitude of 17.6 +/- 3.2 pA (SEM) and a latency of 6.3 +/- 0.5 ms (n = 10). There was a trend for simple excitatory postsynaptic currents (EPSCs) to be evoked in the VLPO cluster, simple inhibitory postsynaptic currents (IPSCs) in the extended VLPO, and a combination of EPSCs and IPSCs in both regions. IPSCs were blocked reversibly by bicuculline (10 microm, n = 11). In both the presence and absence of bicuculline, EPSCs had fast and slow components that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microm; n = 7), and (+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 microm, n = 6), respectively. Reversal potentials for the evoked IPSCs and EPSCs were consistent with mediation via GABAA and ionotropic glutamate receptors, respectively. These results suggest that the SCN region provides both inhibitory and excitatory inputs to single VLPO neurons, which are mediated, respectively, by GABAA receptors and by both non-NMDA and NMDA glutamate receptors. These projections may play important roles in conveying circadian input to systems in the preoptic area that regulate sleep and waking.

Animals↗
PubMed2000

Selective regional blockade of junB gene expression in the hamster suprachiasmatic nucleus by a tyrosine kinase inhibitor.

The hypothalamic suprachiasmatic nucleus (SCN) functions as a circadian pacemaker regulating a variety of physiological and behavioral rhythms in mammals. Retinal illumination evokes expression of several immediate-early genes, including junB, in the ventral SCN early in the subjective night and throughout the SCN later in the subjective night. junB mRNA and protein are also expressed spontaneously around subjective dawn in nocturnal rodents, but only in the dorsal SCN. We examined the biochemical signaling mechanisms underlying both spontaneous and light-evoked expression of junB mRNA in the SCN of Syrian hamsters. Hamsters were injected (i.p.) before subjective dawn with vehicle or with either tyrphostin or genistein, inhibitors of protein tyrosine kinase, and maintained in the dark for 30 min. They were then exposed to a light pulse or kept in darkness for another 30 min. In situ hybridization studies demonstrated that tyrphostin pretreatment (12 or 24 mg/kg) reduced both spontaneous and light-evoked expression of junB mRNA only in the dorsal, and not the ventral, portion of the SCN. Conversely, genistein had little effect on either spontaneous or light-evoked expression of junB mRNA in any part of the SCN. These results indicate that a protein tyrosine kinase sensitive to tyrphostin but not to genistein is involved in the transduction pathways leading to expression of junB mRNA selectively in the dorsal SCN, independently of circadian phase and independently of the involvement of light.

Animals↗
PubMed2000

Electrophysiology and pharmacology of projections from the suprachiasmatic nucleus to the ventromedial preoptic area in rat.

Extracellular and whole-cell patch-clamp recordings were made from neurons in the ventromedial preoptic area in rat horizontal brain slices. Responses to single-pulse electrical stimulation of the ipsilateral suprachiasmatic nucleus were characterized using peristimulus time histograms or postsynaptic current recordings, and bath application of neurotransmitter receptor antagonists. Extracellular recordings showed that suprachiasmatic nucleus stimulation (50-150 microA) elicited a short-latency suppression in 35 of 64 neurons (55%), with the majority (29/35, 83%) showing a biphasic response consisting of a short-latency suppression followed by a long-duration activation. In addition, 14 cells (22%) showed activation only, while 15 (23%) were unresponsive. The GABA(A) receptor antagonist bicuculline (5-10 microM) reversibly blocked suppressions evoked by suprachiasmatic nucleus stimulation (20/20 cells). In the majority of these neurons (13/20), bicuculline also unmasked an activation in response to stimulation. Activations elicited by suprachiasmatic nucleus stimulation, either in the presence or absence of bicuculline, were blocked by the non-N-methyl-D-aspartate and N-methyl-D-aspartate glutamate receptor antagonists 6,7-dinitroquinoxaline-2,3-dione and (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10/10 cells). 6,7-Dinitroquinoxaline-2,3-dione (10 microM) selectively and reversibly blocked the initial, short-duration (<50 ms) activation, but had no effect on the longer-duration activation. In contrast, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10 microM) appeared to inhibit the long-duration activation selectively without affecting the initial rapid activation. Combined applications of the two ionotropic glutamate receptor antagonists blocked stimulation-induced activations completely. All the pharmacological effects were concentration dependent. Whole-cell patch-clamp recordings showed that suprachiasmatic nucleus stimulation elicited inhibitory postsynaptic currents or a combination of inhibitory and excitatory postsynaptic currents in 25 of 33 neurons tested. The inhibitory postsynaptic currents had short onset latencies (4.9+/-0.3 ms) and a reversal potential of -56.0+/-3.8 mV (n=5), and were reversibly blocked by bicuculline (5-10 microM, 4/4 cells). In the presence of bicuculline (5-10 microM), excitatory postsynaptic currents had short onset latencies (4.7+/-0.5 ms), and had a fast and a slow component. (+/-) 3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid blocked the slow, but not the fast, component, whereas 6,7-dinitroquinoxaline-2, 3-dione blocked the fast, but not the slow, component (n=7). These results suggest that the projection from the suprachiasmatic nucleus conveys both inhibitory (GABA) and excitatory (glutamate) inputs to the ventromedial preoptic area. GABA(A) receptor and both non-N-methyl-D-aspartate and N-methyl-D-aspartate glutamate receptors mediate these influences. These inputs may be responsible for conveying information related to circadian phase from the suprachiasmatic nucleus to regions of the preoptic area known to be involved in regulation of sleep/waking and other physiological functions.

Animals↗
PubMed2000

Acute effects of light on body temperature and activity in Syrian hamsters: influence of circadian phase.

Light exposure at night causes an acute increase in human body temperature, which normally falls during the night. This change is largely attributable to the suppression by light of the nocturnal rise in melatonin levels. Little is known, however, about the effects of light on body temperature in nocturnally active mammals in which the nightly peak in melatonin secretion coincides with the circadian phase of elevated, rather than decreased, body temperature. We investigated the effects of a 1-h exposure to light on body temperature and activity of Syrian hamsters, Mesocricetus auratus, at two phases during the night and at two phases during the projected day. Brain or abdominal temperature was recorded continuously using implanted radio transmitters while locomotor activity was monitored simultaneously using a passive infrared movement detector. Responses to light exposure were strongly circadian phase dependent; light during the night caused elevations in both brain and core body temperature, whereas light during the projected day did not. Temperature increases at night could not be attributed solely to activity increases at the onset of light pulses, indicating a contribution from nonbehavioral mechanisms of thermogenesis. These results provide the first evidence for circadian modulation of acute temperature responses to light in a nocturnal mammal.

Animals↗
PubMed2000

Responses of the circadian system of rats to conditioned and unconditioned stimuli.

The circadian systems of rodents respond to light pulses presented during the subjective night with phase shifts and altered cellular activity in the suprachiasmatic nuclei (SCN), including expression of immediate-early genes (IEGs) such as c-fos. A recent study showed that a nonphotic stimulus (an air disturbance generated by a fan) that does not normally induce the expression of c-fos-like immunoreactivity in the SCN of rats can be made to do so after being paired repeatedly with a light pulse in a Pavlovian conditioning paradigm. Furthermore, after conditioning (but not after noncontingent exposure to these stimuli), the fan also induced phase shifts in activity and body temperature rhythms comparable to those produced by light. The authors performed three experiments designed to replicate and extend these findings in rats. In experiment 1, rats were tested for conditioning effects of repeated pairings of a light pulse with a neutral air disturbance under a full photoperiod. In experiment 2, a modified conditioning paradigm was used in which a skeleton photoperiod served as both the entraining zeitgeber and the unconditioned stimulus. Animals in the paired and unpaired training conditions were exposed to both the light pulse and the air disturbance, but the air disturbance signaled the onset of light in the paired condition only. Phase shifts of wheel-running activity rhythms and gene expression in the SCN, intergeniculate leaflet, and paraventricular nucleus of the thalamus were assessed in animals following either of the training conditions or the control procedures. Experiment 3 assessed whether the air disturbance could entrain the circadian activity rhythms of rats with or without previous pairing with light in a classical conditioning paradigm. No evidence for classical conditioning, nor for unconditioned effects of the air disturbance on the circadian system, was found in these studies.

Air↗
PubMed1999

Differential effects of glutamatergic blockade on circadian and photic regulation of gene expression in the hamster suprachiasmatic nucleus.

Nocturnal light exposure induces immediate-early gene (IEG) expression in the hypothalamic suprachiasmatic nucleus (SCN) and causes phase shifts of activity rhythms in mammals. Some IEGs also show a circadian rhythm of expression in the SCN. While excitatory amino acids (EAAs) are known to be involved in mediating photic regulation of entrainment and gene expression, their involvement in spontaneous rhythms of gene expression has not been studied. We assessed the role of NMDA receptors in the expression of NGFI-A, junB and fosB mRNAs induced by light pulses of different intensities late in the night (Zeitgeber Time [ZT] 18). We also examined the spontaneous expression of junB mRNA near subjective dawn (ZT 0). Both dim (5 lx) and bright (100 lx) light pulses induced similar levels of expression of NGFI-A and junB in the SCN late in the night. fosB mRNA was strongly induced by bright light but was less sensitive to dim light. At ZT 18, dizocilpine (MK-801) (3 mg/kg, i.p. ), a non-competitive NMDA receptor antagonist, almost completely blocked light-evoked expression of IEG mRNAs in the ventral SCN but not in the dorsolateral region at a mid-caudal level using either light intensity. At ZT 0, MK-801 strongly reduced light-evoked expression of junB mRNA in both SCN subdivisions, but inhibited spontaneous expression significantly only in the dorsal region. NMDA receptors appear to play an important role in mediating photic input regulating IEG expression only in the ventral SCN at night. At dawn, however, NMDA receptors are involved in mediating photic effects in both parts of the SCN, as well as being involved in spontaneous activation of junB expression selectively in the dorsal SCN. These findings support the idea that the effects in the dorsolateral SCN of nocturnal light exposure are mediated by different mechanisms than those in other portions of the nucleus.

Animals↗
PubMed1999

Photic responses of suprachiasmatic area neurons in diurnal degus (Octodon degus) and nocturnal rats (Rattus norvegicus).

Photic sensitivity of cells in the suprachiasmatic nuclei (SCN), the principal pacemaker of the mammalian circadian system, has been documented in several species. In nocturnal rodents, the majority of photically responsive SCN cells are activated by retinal illumination. One report identified mostly photic suppressions among SCN cells in a diurnal rodent, studied under somewhat different conditions. We examined photic sensitivity of SCN cells in a predominantly diurnal rodent, the degu, studied in vivo under identical conditions to rats, and found that a large majority of photic SCN cells were suppressed by light. In both rats and degus, SCN cells were more responsive to light during the subjective night than during the subjective day. Light-responsive cells did not show a daily rhythm in baseline firing rates in either species, but rat SCN cells that did not respond to light were more active spontaneously during the subjective day. Light-unresponsive SCN cells in degus did not show a similar pattern. There are substantial differences in the neurophysiological activity and photic responsiveness of SCN cells in diurnal degus and nocturnal rats.

Animals↗
PubMed1999

Circadian and photic regulation of immediate-early gene expression in the hamster suprachiasmatic nucleus.

The hypothalamic suprachiasmatic nucleus is the site of an endogenous circadian clock synchronized by daily light-dark cycles. At some daily phases, light exposure both shifts the clock and alters the expression of several immediate-early genes in cells of the suprachiasmatic nucleus. We have studied both spontaneous circadian and light-induced expression of several immediate-early gene messenger RNAs and proteins in hamsters in constant darkness or in response to brief light exposure. There was no detectable spontaneous expression of NGFI-A messenger RNA in suprachiasmatic nucleus cells at any circadian phase, but light pulses induced its expression selectively during the subjective night, with highest levels of expression 6 h into the night. We also found that there are two independent rhythms of expression of junB messenger RNA and JunB protein, as well as c-fos messenger RNA and c-Fos protein, in the suprachiasmatic nucleus of hamsters: a rhythm of photic sensitivity expressed throughout the night and a spontaneous rhythm of expression triggered around dawn. Induction of NGFI-A messenger RNA and c-fos messenger RNA and c-Fos protein in response to a light pulse were found throughout the suprachiasmatic nucleus, with the highest levels of expression in the ventrolateral subdivision; however, the spontaneous expression of JunB and c-Fos proteins was confined mainly to the dorsomedial suprachiasmatic nucleus. The temporal and anatomical differences in the expression of these immediate-early genes in the mammalian suprachiasmatic nucleus suggest that their protein products may be involved in different signaling mechanisms mediating either photic entrainment or endogenous oscillations within distinct subpopulations of suprachiasmatic nucleus cells.

Animals↗
PubMed1999

Daily rhythm of spontaneous immediate-early gene expression in the rat suprachiasmatic nucleus.

Nocturnal light induces the expression of various immediate-early genes (IEGs) in the suprachiasmatic nucleus (SCN), the primary pacemaker of the circadian system of mammals, and causes phase shifts of behavioral rhythms. In the hamster SCN, some IEGs show both sensitivity to light induction at night and a daily peak of spontaneous expression near dawn in different regions of the nucleus. To investigate whether both patterns of IEG expression are observed in the rat SCN, the authors studied the expression of NGFI-A, junB, c-fos, and fosB near the time of subjective dawn in rats entrained to a light-dark 12:12 cycle and then maintained in constant total darkness for approximately 48 h. They found that there were two independent rhythms of expression for junB and c-fos mRNAs in the SCN: (1) a rhythm of photic sensitivity expressed throughout the night and (2) a spontaneous rhythm of expression triggered around dawn and persisting for at least 2 h into the day. By contrast, fosB and NGFI-A transcripts were expressed only after light exposure at night and did not exhibit significant levels of spontaneous expression in the absence of photic input. These observations demonstrate that the circadian clock gates expression of two independent rhythms related to IEG expression in the rat SCN. The rhythm of sensitivity to nocturnal light exposure is expressed more strongly in the ventral SCN and may be related to photic entrainment. The second rhythm is triggered spontaneously in darkness around subjective dawn and is expressed in more dorsal parts of the SCN.

Animals↗
PubMed1998

Daily variation of muscarinic receptors in visual cortex but not suprachiasmatic nucleus of Syrian hamsters.

Intraventricular administration of carbachol can induce phase shifts in wheel-running activity in rodents, which depend on circadian phase and are mediated via muscarinic cholinergic receptors in Syrian hamsters. We studied the circadian variation in binding of [3H]-N-methylscopolamine ([3H]NMS), a hydrophilic muscarinic receptor antagonist, in micropunches obtained from the anterior hypothalamus and occipital cortex of Syrian hamsters housed in a 14:10 light:dark cycle. Binding sites were characterized on cells contained within 1 mm punches (obtained from slices 300 microm thick), using a method to selectively detect cell surface (functional) receptors. Atropine sulphate was used to determine nonspecific binding. Cortex showed a significant daily rhythm in [3H]NMS binding with a peak occurring late in the light phase and a trough at lights on, while the hypothalamus showed no detectable rhythm. Following suprachiasmatic nucleus (SCN) ablation or maintenance in constant darkness, the rhythm in the cortex was abolished. These findings suggest that photic information conveyed via the SCN is responsible for the receptor binding rhythm in the cortex. Autoradiographic studies ([3H]NMS; 2 nM, 3 weeks exposure) clearly revealed both M1 and M2 subtypes of muscarinic receptors in the region of the SCN and the visual cortex.

Animals↗
PubMed1998

Actions of histamine in the suprachiasmatic nucleus of the Syrian hamster.

Previous studies have suggested a role for histamine in mediating effects of light on rodent circadian systems. We combined behavioural and neuroanatomical studies to analyze the potential role of histamine in circadian rhythm regulation of Syrian hamsters. The effects of histamine and the selective H2 receptor agonist dimaprit on free-running locomotor activity rhythms were monitored. In addition, histamine projections were mapped immunohistochemically. Histamine (0.5 microl of 1 mM) microinjected into the region of the suprachiasmatic nucleus induced very small delay phase-shifts, which were significantly greater than those elicited by vehicle at circadian time (CT) 18. No other significant differences were observed. Dimaprit (0.5 microl of 1 mM) microinjected into the region of the suprachiasmatic nucleus at CT 6 and CT 18, induced very small phase-shifts which were significantly different from the effects of vehicle, but did not resemble those of light. Numerous cell bodies immunopositive for histamine were found in the tuberomammillary nucleus of the posterior hypothalamus, while histamine immunoreactive fibres were seen in the periventricular nucleus and paraventricular nucleus of the anterior hypothalamus. The suprachiasmatic nuclei were largely devoid of immunostaining. Finally, preliminary electrophysiological studies demonstrated that ionophoretic application of histamine and the H2 receptor agonist dimaprit elicit inconsistent and weak responses in the hamster suprachiasmatic nucleus in vitro. The results presented here show that microinjections of HA or dimaprit into the SCN region do not mimic the effects of light on hamster circadian rhythms, and the SCN of the Syrian hamster is almost devoid of histaminergic fibres. These studies suggest that histamine does not play a prominent role in circadian rhythm regulation in this species.

Animals↗