Biomedical subjects

J T Pan

Publications and source records attributed to J T Pan.

At least 37 records · Page 2Linked to original sources

PubMed1996

Effects of natriuretic peptides and dopamine on single-unit activity of dorsomedial arcuate neurons in rat brain slices.

The effects of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) on single-unit activity of dorsomedial arcuate (DM-ARC) neurons were reported. The modulatory effect of CNP on dopamine's (DA) action was also studied. ANP alone in 0.05-0.5 nmol doses induced 26% inhibition and 14% excitation of 37 DM-ARC neurons; the majority (60%) were not responsive. CNP, however, inhibited 46% and excited 4% of 74 DM-ARC neurons. Dose-dependent inhibitory effects of CNP were also observed. In 71 neurons tested with both CNP and DA, more neurons were inhibited by DA (66%) than those by CNP (46%). About one-third (34%) of them were inhibited by both. Furthermore, in 41 neurons inhibited by DA, more than half (54%) of their responses were potentiated by co-administration of CNP. In conclusion, CNP by itself exhibited a predominantly inhibitory action on DM-ARC neurons; and it also potentiated the inhibitory effect of DA on these neurons.

Animals↗

PubMed1996

Prolonged pertussis toxin treatment affects morphine's action on tuberoinfundibular dopaminergic neuron activity and on prolactin secretion.

The effects of pertussis toxin (PTX) pretreatment on basal and morphine-affected changes of tuberoinfundibular dopaminergic (TIDA) neuron activity and serum prolactin level were tested in this study. Adult female Sprague-Dawley rats, ovariectomized and treated with a long-acting estrogen (polyestradiol phosphate, 0.1 mg/rat, s.c.), were used. The activity of TIDA neurons was determined by measuring the turnover rate of dopamine (DA), and the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylalanine (DOPA) in the median eminence. Acute (30-90 min) treatment of PTX had no significant effect on any of the parameters measured. Prolonged (24 h) treatment of PTX significantly reduced morphine's inhibitory effect on TIDA neuron activity (using DOPA, but not DOPAC as the index), and stimulatory effect on PRL release. Basal TIDA neuron activity as determined by median eminence DOPAC concentration, DOPA accumulation, or DA rate constant was not significantly altered by PTX. Median eminence DA level, however, was significantly reduced. These results suggest that a pertussis toxin-sensitive GTP-binding protein may be responsible for the maintenance of TIDA neurons, and for mediation of the inhibitory effect of morphine on TIDA neuron activity, and in turn, the stimulation of prolactin secretion.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Central administration of 8-OH-DPAT and mCPP stimulates prolactin secretion in ovariectomized, estrogen-treated rats: lack of an effect on tuberoinfundibular dopaminergic neuron activity.

The effects of central administration of two serotonin receptor agonists, 8-OH-DPAT and mCPP, on tuberoinfundibular dopaminergic (TIDA) neuron activity and serum prolactin (PRL) levels in ovariectomized, estrogen-treated rats were determined. 8-OH-DPAT dose-dependently (0.1-10 microgram/rat, icv) stimulated serum PRL levels, and depressed serotonergic neuron activity in 30 min. However, the TIDA neuron activity was not affected at all. Similar treatment of mCPP was less effective than 8-OH-DPAT: only the highest dose of mCPP (10 microgram) stimulated PRL secretion and inhibited serotonergic neuron activity. No change in TIDA neuron activity was observed either. We conclude that central serotonin acts on 5-HT1 receptors to stimulate the PRL secretion, which may not involve the TIDA neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Sexual differences in the diurnal changes of tuberoinfundibular dopaminergic neuron activity in the rat: role of cholinergic control.

A diurnal change of the tuberoinfundibular dopaminergic (TIDA) neuron activity in ovariectomized rats treated with or without estrogen was recently reported, and the endogenous cholinergic system may be responsible for its induction. Whether a similar rhythm exists in intact female or male rats was the focus of this study. TIDA neuron activity was assessed by measurement of the precursor or metabolite of dopamine in the median eminence by HPLC with electrochemical detection. In intact female Sprague-Dawley rats, diurnal changes in TIDA neuron activity were observed during all stages of the estrous cycle, i.e., proestrus, estrus, and diestrus 1, and they were nearly identical. No such rhythm, however, was observed in intact male rats. Castration alone decreased and increased basal TIDA neuron activity in female and male rats, respectively, and estrogen treatment increased the activity in both sexes. The diurnal changes in TIDA neuron activity, however, were observed only in the female rats, not the male rats, regardless of castration or estrogen treatment. Serum prolactin levels in the male rats exhibited no diurnal changes either, irrespective of whether the animals had been castrated or treated with estrogen. Central administration of mecamylamine (1 micrograms/3 microliters per rat, i.c.v.), a nicotinic receptor antagonist, in the morning (at 1000 h) or afternoon (at 1500 and 1700 h) induced a differential effect on the TIDA neuron activity of intact female rats, i.e., no effect in the morning and stimulation in the afternoon; it had no effect on the TIDA neuron activity in the male rats regardless of the injection time. In castrated male rats treated with estrogen, however, mecamylamine treatment further increased TIDA neuron activity, but still with no diurnal difference. In summary, a sexual difference in the diurnal changes of TIDA neuron activity was observed, and these changes may be under differential control by the cholinergic system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Stimulatory effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide on tuberoinfundibular dopaminergic neuron activity in estrogen-treated ovariectomized rats and their correlation with prolactin secretion.

The effects of central administration of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) on hypothalamic tuberoinfundibular dopaminergic neuron activity and serum prolactin (PRL) levels were reported. Adult female Sprague-Dawley rats overiectomized for 2 weeks, implanted with subcutaneous estrogen-containing capsules and intracerebroventricular (i.c.v.) cannulae for 6 days were used for experiments. I.c.v. injections of VIP or PACAP were performed in conscious rats in the morning, and the injected rats were decapitated at various times afterwards. Serum sample and the median eminence tissue were collected from each rat. The levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylalanine (DOPA) in the median eminence were determined by high-performance liquid chromatography with electrochemical detection. Serum PRL levels were determined by radioimmunoassay. I.c.v. administration of VIP (1 microgram/3 microliter) significantly increased median eminence DOPAC/DA ratio at 30 min, and serum PRL level at 15 min. The same dose of VIP (1 microgram), but not higher (10 micrograms) or lower (0.1 microgram), was also effective in stimulating the median eminence DOPA accumulation 35 min after the injection. The effect of VIP (1 microgram) on median eminence DOPA could be blocked by coadministration of a VIP antagonist, VIP6-28 in 10- and 30-, but not in 1- or 0.1-microgram doses. On the other hand, i.c.v. administration of PACAP (10 micrograms) stimulated median eminence DOPAC and lowered serum PRL levels at 30 min. All doses of PACAP used (0.1, 1 and 10 micrograms/ rat, i.c.v.) significantly increased median eminence DOPA concentrations at 60 min. The stimulatory effect of PACAP (0.1 microgram) on median eminence DOPA could also be blocked by coadministration of a PACAP antagonist, PACAP6-38 (in 10 to 100 x higher doses). In summary, central administration of either VIP or PACAP exhibited a stimulating effect on TIDA neuron activity through specific receptors. Serum PRL levels, however, were stimulated and inhibited by VIP and PACAP, respectively.

Animals↗

PubMed1996

Stimulatory effect of central oxytocin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretion: neurochemical and electrophysiological studies.

The posterior pituitary hormone, oxytocin (OT), has been shown to have either a stimulatory or an inhibitory effect on PRL secretion depending on the route of administration. Whether its central inhibitory effect involves the tuberoinfundibular dopaminergic (TIDA) neuron was the focus of this study. Adult female Sprague-Dawley rats ovariectomized for 1 week, implanted with sc estrogen-containing capsules and intracerebroventricular cannulas for 6 more days were used. TIDA neuron activity was determined by measuring the concentration of 3,4-dihydroxyphenylacetic acid or 3,4-dihydroxyphenylalanine in the median eminence by HPLC with electrochemical detection. Intracerebroventricular injection of OT induced both dose (0.01-1 microgram/rat)- and time (30-90 min)-dependent increases in 3,4-dihydroxyphenylalanine or 3,4-dihydroxyphenylacetic acid levels in the median eminence. Serum PRL levels were also decreased 30 min after the injection. The use of a specific OT antagonist, [d(CH2)5, Tyr(Me)2, Orn8]vasotocin, not only blocked the effect of OT on TIDA neuron activity, it further lowered it to below control levels, indicating the existence of an endogenous OT activity. When 1 microgram OT was administered at 1200 h, it also reversed the diurnal decrease in TIDA neuron activity at 1500 h. The effects of OT on the electrical activities of dorsomedial arcuate neurons were also tested using single unit recording in brain slices. In 33 neurons tested with OT, 66.7% were stimulated by OT in 0.5- to 50-nmol doses, and no inhibitory effect was observed. The rest were not responsive. In conclusion, both neurochemical and electrophysiological studies demonstrated that central OT may play a stimulatory role in regulating the TIDA neurons and, in turn, inhibition of PRL secretion.

Animals↗

PubMed1996

Cancer of the gingiva, buccal mucosa, and palate.

While most cases of intraoral cancer arise in the cancer-prone horseshoe comprised of the floor of the mouth, the posterolateral borders and ventral surface of the tongue, and the retromolar region, no intraoral site is immune. This article reviews the clinical features of squamous cell carcinoma of the gingiva, buccal mucosa and palate, as well as the less common oral malignancies that can arise at these intraoral sites.

Carcinoma, Squamous Cell↗

PubMed1995

Differential effects of angiotensin II on the activities of suprachiasmatic neurons in rat brain slices.

The effects of angiotensin II (AII) on the firing rates of suprachiasmatic neurons were determined in rat brain slices. AII in pmol ranges stimulated 25% and inhibited another 25% of 52 irregular firing neurons, while it stimulated 23% and inhibited 4% of 30 regular firing neurons. Three "oscillating" neurons whose firing rates oscillated with rather constant amplitudes and periods were recorded. AII induced the occurrence of oscillation in one unit and modulated the oscillation amplitude of the other two. Pretreatment with saralasin, an AII antagonist, effectively blocked (100%) the actions of AII (n = 5). The present findings suggest that AII may act as an important mediator in the suprachiasmatic nucleus and its mode of action may be variable in different neurons.

Angiotensin II↗

PubMed1995

Effects of endogenous opioid peptides and their analogs on the activities of hypothalamic arcuate neurons in brain slices from diestrous and ovariectomized rats.

Various endogenous opioid peptides and some of their analogs were used in this study to test their effects on the membrane activities of hypothalamic arcuate neurons in brain slices. Both ovariectomized and diestrous rats were used in the study, and freshly prepared brain slices from these animals were used for extracellular single-unit recording studies. All of the opioids exhibited potent inhibitory effects on the firing of arcuate neurons, viz., beta-endorphin inhibited 55% (n = 33), DAGO 62% (n = 21), dynorphin A 55% (n = 11), U50,488 36% (n = 39), Met-enkephalin 35% (n = 54), and DPDPE 50% (n = 8) of tested arcuate neurons from ovariectomized rats. Significantly higher percentage of inhibition was observed in slice preparations from diestrous rats for DAGO 86% (n = 22), and slightly higher for dynorphin A 59% (n = 22) and U50,488 53% (n = 15). Pretreatment with naloxone prevented most of the actions by beta-endorphin and DAGO, and nor-binaltorphimine prevented those by dynorphin A and U50,488. Most of the effects of Met-enkephalin could also be blocked by nor-binaltorphimine (67%, n = 6), but less by naltrindole (25%, n = 8). Naltrindole, however, seemed to be more effective in blocking the action of [D-Pen2,5]-enkephalin (100%, n = 2). In summary, all opioids tested exerted potent inhibitory effects upon the firing of arcuate neurons possibly through multiple opioid receptors, and the presence of ovarian hormones may have an effect on the neuron's responsiveness to opioid acting on mu type receptors.

Animals↗

PubMed1995

Bombesin acts in the suprachiasmatic nucleus to affect circadian changes in tuberoinfundibular dopaminergic neuron activity and prolactin secretion.

Central administration of bombesin has been shown to block the afternoon PRL surge. A circadian change in the activity of tuberoinfundibular dopaminergic (TIDA) neurons that coincides with the onset of the PRL surge has also been found. Whether bombesin acts on the TIDA neuron to affect the PRL surge and where bombesin acts were the focuses of this study. Bombesin (0.75 microgram/3 microliters.rat) was first injected into the lateral cerebroventricle of estrogen-primed ovariectomized rats at 1200 h through preimplanted cannulas. Both the PRL surge and the circadian changes in TIDA neuron activity (using both 3,4-dihydroxyphenylacetic acid concentration and 3,4-dihydroxyphenylalanine accumulation in the median eminence as indexes) were blocked by the treatment. In suprachiasmatic nucleus-lesioned rats, however, both rhythms were absent, and the injection of bombesin exhibited no significant effect. Using microinjection of bombesin (50 ng/0.2 microliter) bilaterally into either the suprachiasmatic or arcuate nuclei at 1200 h, only the former injection effectively blocked both TIDA neuron activity and the PRL surge. We conclude that bombesin may act on the rhythm generation center, the suprachiasmatic nucleus, to exert its effect to disrupt TIDA neuron activity and the PRL surge.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

An endogenous cholinergic rhythm may be involved in the circadian changes of tuberoinfundibular dopaminergic neuron activity in ovariectomized rats treated with or without estrogen.

We recently reported that a circadian change in the activities of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons exists in ovariectomized (OVX) rats treated with or without estrogen. The involvement of an endogenous cholinergic control mechanism was the focus of this study. Adult female Sprague-Dawley rats OVX for 2 weeks and treated with or without a long-acting estrogen (poly-estradiol phosphate, 0.1 mg/rat, sc) were used in the study. An intracerebroventricular cannula for drug injection was implanted into the lateral cerebroventricle of each rat 6 days before experiment. TIDA neuron activity was determined by measuring the concentrations of 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylalanine in the median eminence by HPLC plus electrochemical detection. Serum PRL levels were determined by RIA. Neither atropine nor mecamylamine, two cholinergic receptor antagonists, had any effect on TIDA neuron activity in the morning before 1200 h, when endogenous TIDA neuron activity is high. Both drugs, however, exhibited a dose-related stimulating effect on the TIDA neuron activity in the afternoon, when endogenous activity is low. The estrogen-induced afternoon PRL surge was also blocked by a single injection of atropine or mecamylamine at 1300 h. The rhythmic changes in endogenous TIDA neuron activity and their responses to atropine were also observed in OVX rats with no estrogen replacement. In conclusion, a daily change in endogenous cholinergic neuron activity may be responsible for the change in TIDA neuron activity in female rats, which is a prerequisite for the PRL surge.

Animals↗

PubMed1994

Differential neuronal responses to angiotensin III from the subfornical organ of normotensive and spontaneously hypertensive rats.

We previously reported that chronic central administration of angiotensin III (AIII) fails to produce sustained drinking behavior in spontaneously hypertensive rats (SHR), possibly because of the development of early desensitization of the angiotensin receptors. The present study extended these findings to the cellular level, using brain-slice preparation from Wistar-Kyoto rats (WKY) and SHR, in conjunction with single-neuron recording in the subfornical organ (SFO), a target site for angiotensin II-induced drinking. We found that a majority of the SFO neurons studied (13/18 in WKY, 20/28 in SHR) responded in a dose-related manner to AIII, given in the range of 10(-6)-10(-5) M. This excitation was receptor-specific, since it was reversed by Ile7-AIII (10(-4)-10(-3) M), the selective AIII antagonist. Bestatin (10(-5)-10(-4) M), an aminopeptidase B inhibitor, did not discernibly affect basal spike frequency when delivered alone. Nevertheless, given in combination with the heptapeptide, bestatin reduced the intensity and duration of SFO neuronal response in WKY to the higher dose (10(-5) M), and in SHR to both doses (10(-6) or 10(-5) M), of AIII. These data suggest that the SFO may also be a central site of action for AIII. Moreover, prolonging the action of AIII by protecting it from being metabolized with bestatin may produce desensitization of the angiotensin receptors on SFO neurons. This was particularly so in the SHR, which are thought to be defective in the degradation of the heptapeptide in the brain.

Aminopeptidases↗

PubMed1994

Stimulatory effects of bombesin-like peptides on hypothalamic arcuate neurons in rat brain slices.

The effects of bombesin, gastrin-releasing peptide, neuromedin C, ranatensin, and neuromedin B on hypothalamic arcuate neurons were tested in this study using extracellular single-unit recording in fresh brain tissue slices. Adult ovariectomized Sprague-Dawley rats were used for preparation of brain slices. All bombesin-like peptides in pmol ranges exhibited potent stimulatory effects on the firing of arcuate neurons, i.e., gastrin-releasing peptide stimulated 90.9% (n = 22), bombesin 78.0% (n = 41), neuromedin C 63.2% (n = 19), ranatensin 58.0% (n = 22), and neuromedin B 50.0% (n = 6) of arcuate neurons tested. Pretreatments with either [Leu13-psi(CH2NH)-Leu14]-bombesin or [D-Phe6,Des-Met14]-bombesin6-14 ethylamide, two bombesin antagonists, significantly blocked most of the actions of bombesin-like peptides tested. The present results further support the notion that bombesin-like peptides may play a significant role in the arcuate nucleus.

Animals↗

PubMed1994

Enhanced tuberoinfundibular dopaminergic neuron activity in thyroidectomized, ovariectomized and estrogen-treated rats with hyperprolactinemia.

The involvement of the tuberoinfundibular dopaminergic (TIDA) neurons in the genesis of hyperprolactinemia in female thyroidectomized rats treated with estrogen was the focus of this study. Rats that were ovariectomized (3 weeks), thyroidectomized (2 weeks) and treated with estrogen for 6 days had a 5- to 10-fold increase in serum prolactin (PRL) levels, while the rats receiving the same treatments but without estrogen had lower PRL levels. The activity of TIDA neurons, using dihydroxyphenylacetic acid (DOPAC) concentration or the DOPAC/dopamine (DA) ratio in the median eminence (ME) as an index, was increased and decreased in estrogen-treated and untreated rats, respectively. The increases in serum PRL level and the activity of TIDA neurons were dependent on the duration of thyroidectomy and could both be lowered by daily injection of thyroid hormone (20 or 100 micrograms/kg b.w. thyroxine, i.p.) for 12 days in a dose-dependent manner. Using dihydroxyphenylalanine (DOPA) accumulation in the ME as another index, we also found an increased DOPA/DA ratio in estrogen-treated hypothyroid rats, which effect could be reversed by replacement of thyroid hormone. Furthermore, treatments with bromocryptine (3 mg/kg b.w./day, s.c.) for 3 days or with cysteamine (100 mg/kg b.w., s.c.) at 26, 15 and 2 h before the rats were sacrificed lowered both serum PRL level and TIDA neuron activity. Since PRL can exert a short-loop feedback control on its own secretion, these results indicate that the increased serum PRL levels in estrogen-treated hypothyroid female rats should be the cause, but not the result, of the increased activity of TIDA neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Circadian changes of serum prolactin levels and tuberoinfundibular dopaminergic neuron activities in ovariectomized rats treated with or without estrogen: the role of the suprachiasmatic nuclei.

Variations of serum prolactin (PRL) levels and activities of tuberoinfundibular dopaminergic (TIDA) neurons during the afternoon of ovariectomized (OVX) rats treated with or without estrogen were determined in this study. Long-term OVX rats treated with or without polyestradiol phosphate (0.1 mg/rat, s.c.) were decapitated every hour from 10.00 to 19.00 h (except 11.00 and 13.00 h). Serum PRL and median eminence (ME) dihydroxyphenylacetic acid (DOPAC) or dihydroxyphenylalanine (DOPA) levels were determined by radioimmunoassay and high performance liquid chromatography plus electrochemical detection, respectively. A prominent PRL surge started and peaked around 14.00-15.00 h, and remained significantly higher than levels of 10.00 and 12.00 h throughout the afternoon. Significant decreases of ME DOPAC and DOPA concentrations were also observed between 14.00 and 19.00 h. In OVX rats with no estrogen replacement, no PRL surge was observed and the changes of ME DOPAC concentrations during the afternoon were not significant except for that at 17.00 h. The ME DOPA accumulation, however, exhibited significantly lower levels from 14.00 to 19.00 h than that at 12.00 h, indicating that an endogenous rhythm for DA synthesis existed in OVX rats. In estrogen-treated OVX rats bearing bilateral lesions of the suprachiasmatic nuclei, both changes in serum PRL level and TIDA neuron activity were abolished. We conclude that an endogenous rhythm of the activities of TIDA neurons may exist in both OVX and OVX plus estrogen-treated rats. The rhythm is regulated by the suprachiasmatic nuclei and may be amplified by estrogen for the induction of PRL surge.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Correlation between prolactin secretion and Gs protein expression during sustained cholera-toxin stimulation.

We have studied the chronic effect of cholera toxin (CTX) on prolactin synthesis and secretion in GH3 pituitary-tumour cells. Time-course analysis showed that prolactin secretion increased with time of CTX exposure, reached a peak at 3 h, and decreased thereafter. Prolactin synthesis was also shown to be stimulated by CTX. The basic and forskolin-stimulated cyclic AMP levels of the CTX-treated cells followed a biphasic time response similar to that of prolactin secretion. Exposure of cells to CTX for more than 3 h abolished the subsequent CTX-catalysed ADP-ribosylation in vitro. Moreover, a significant decrease in the pertussis-toxin-catalysed ADP-ribosylation was found after cells were exposed to CTX for longer than 6 h. Western-blot analysis indicated that the amount of Gs alpha (alpha-subunit of Gs) protein increased within 3 h, followed by a gradual decrease to 50% of the control level at 24 h. The accumulation of Gs alpha mRNA increased within 6 h of CTX exposure, and decreased thereafter to 40% of the basal level at 48 h. Our findings that prolonged treatment of CTX induced similar patterns of time responses in Gs alpha protein expression, cyclic AMP production and prolactin secretion indicate that CTX-induced changes in Gs alpha protein levels may be responsible for the cellular response leading to prolactin secretion.

Adenosine Diphosphate Ribose↗

PubMed1993

Effects of systemic administration of 6-hydroxydopamine, 6-hydroxydopa and 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) on tuberoinfundibular dopaminergic neurons in the rat.

Using systemic route of administration, the effects of several neurotoxins on hypothalamic tuberoinfundibular dopaminergic neurons were focused in this study. 6-Hydroxydopamine (6-OHDA, 10 or 100 mg/kg b.wt., i.v. or ip) produced a dose (37 vs. 50%)- and time (41 to 29% from day 4 to day 9)-dependent depletion of hypothalamic median eminence dopamine concentrations, and increases of serum prolactin levels in ovariectomized rats. Other central dopaminergic neurons, however, were not significantly affected. Similar treatments with 6-hydroxydopa (6-OHDOPA) were less effective. On the other hand, treatments of 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP, 10 mg/kg b.wt./day, ip) for 7 or 14 days produced significant decreases of dihydroxyphenylacetic acid (DOPAC) levels in the median eminence and periventricular regions, and increases in serum prolactin levels. Other central dopaminergic neurons were not significantly affected, though. These results suggest that systemic administration of 6-OHDA, 6-OHDOPA, or MPTP, can produce specific destructive effects on the tuberoinfundibular dopaminergic neurons.

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

PubMed1993

Potentiating effects of serotonin and vasoactive intestinal peptide on the action of glutamate on suprachiasmatic neurons in brain slices.

Using extracellular single-unit recording in brain slices, we have tested the effects of serotonin and vasoactive intestinal peptide (VIP) on the action of glutamate on hypothalamic suprachiasmatic neurons. We hypothesized that serotonin and VIP may interact with glutamate so that a modulation of the circadian rhythm entrainment to the light-dark may be possible. Given individually, glutamate excited 32% and inhibited 1% (n = 65), serotonin excited 8% and inhibited 27% (n = 73), and VIP excited 7% and inhibited 7% (n = 41) of suprachiasmatic neurons. When administered together, however, serotonin or VIP not only increased the percentage of neurons (up to 50%) that responded to glutamate, but also potentiated the neuronal responses to glutamate. These findings substantiated our hypothesis that both serotonin and VIP may modulate the action of glutamate in the suprachiasmatic nucleus.

Animals↗