Biomedical subjects

D A Morilak

Publications and source records attributed to D A Morilak.

At least 37 records · Page 2Linked to original sources

PubMed1993

Ontogeny of 5-hydroxytryptamine2 receptor immunoreactivity in the developing rat brain.

In this study, we investigated the regional and temporal emergence of 5-hydroxytryptamine2 receptor immunoreactivity in the developing rat brain. In a qualitative immunocytochemical analysis using an antibody against the rat 5-hydroxytryptamine2 receptor protein, we visualized cells expressing the receptor in the pontine tegmentum, caudate nucleus, basal forebrain, hippocampus and neocortex of developing rats. Three potentially important periods in the developmental regulation of 5-hydroxytryptamine2 receptors were identified: the time of onset, a period of accelerated expression and hyper-elaboration, and a period of regression. In general, the onset of 5-hydroxytryptamine2 receptor immunoreactivity occurred relatively late in the ontogeny of cells in these regions, in the late prenatal and early postnatal periods. Following the perinatal onset of receptor expression, there was a rapid increase in the number of immunoreactive neurons during the first week after birth. In neocortex, there appeared to be a relative over-expression of the receptor, with an elevated density and hyper-elaboration of immunopositive neurons relative to the adult, reaching a peak at the end of the second week. There was then a gradual decrease in both the density and morphological complexity of cortical 5-hydroxytryptamine2-labelled neurons, until the adult pattern of expression was achieved at about four weeks of age. In all areas studied, cells positive for the 5-hydroxytryptamine2 receptor were first detected within the regions in which they would ultimately reside, and after the known periods of cell proliferation for these regions. These observations would argue against a role for the 5-hydroxytryptamine2 receptor as a transducer of the early developmental influences of serotonin in the central nervous system, but leave open the possibility that the receptor may participate in regulating some aspect of terminal differentiation or late maturation of the neurons on which it is found. The identification of important developmental periods in the ontogeny of 5-hydroxytryptamine2 receptors suggests time-points at which events that disrupt the normal ontogenetic pattern of expression could produce long-lasting effects on central serotonergic neurotransmission.

Animals↗

PubMed1991

Endogenous opioids tonically inhibit the depressor neurones in the caudal ventrolateral medulla of rabbits: mediation through delta- and kappa-receptors.

In the present studies, an attempt was made to elucidate the role of endogenous opioid inputs to the depressor region of the caudal ventrolateral medulla in the tonic regulation of arterial pressure and to examine the subtype(s) of receptor underlying any observed effects by use of receptor-specific antagonists. The depressor region of the caudal ventrolateral medulla in chloralose-anesthetized, artificially ventilated rabbits was functionally identified by injection of l-glutamate (5 nmol). Bilateral injection of the non-selective opioid antagonist naloxone (0.3, 5 and 20 nmol) into the caudal ventrolateral medulla produced a dose-dependent depressor response, accompanied by a bradycardia, suggesting a tonically active inhibitory opioid input to this region. Bilateral injection of the selective delta-receptor antagonist ICI 174,864 (0.3 nmol) or of the kappa-receptor antagonist nor-binaltorphimine (1 nmol), also markedly reduced both arterial pressure and heart rate. In contrast, injection of the mu-selective antagonist beta-funaltrexamine (0.3-0.6 nmol) produced no effect on arterial pressure or heart rate. These data support the hypothesis that tonically active endogenous opioid inputs, possibly enkephalinergic and/or dynorphinergic, inhibit the depressor neurones of the caudal ventrolateral medulla in the rabbit through activation of delta- and kappa-receptors. Surprisingly, injection of the opioid agonists leu-enkephalin (1 nmol) or dynorphin 1-13 (0.1 nmol), but not the selective mu-receptor agonist DAGO (1 nmol), in the depressor area of the caudal ventrolateral medulla also induced naloxone-sensitive (5 mg/kg, i.v.) decreases in both arterial pressure and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1991

Opioid innervation of the caudal ventrolateral medulla is not critical for the expression of the aortic depressor nerve response in the rabbit.

We investigated the influence of endogenous opioids in the caudal ventrolateral medulla (CVLM) on the expression of the baroreflex response induced by the electrical stimulation (50 Hz, 0.2 ms, 11 V, 10 s) of the aortic depressor nerve. We used microinjection of selective opioid antagonists into the functionally identified depressor area of the CVLM in chloralose-anesthetized rabbits. Injection of vehicles or the mu-antagonist beta-funaltrexamine (0.3 nmol) into the CVLM had no effects, while naloxone (20 nmol), ICI 174,864 (delta-antagonist, 0.3 nmol) or nor-binaltorphimine (kappa-antagonist, 1 nmol) abolished the depressor response, but themselves all elicited a tonic depressor effect as well. In contrast, intravenous naloxone (5 mg/kg) induced a small but significant increase in arterial pressure and did not alter the depressor response. Hypotensive hemorrhage induced a decrease in arterial pressure similar to that seen with local injection of naloxone into the CVLM, but did not change the reflex, suggesting that the reflex abolition was not due to the decrease in basal arterial pressure per se. CVLM injection of glutamate (10 nmol) or the GABA-antagonist bicuculline (0.1 nmol), non-opioid agents which activate CVLM and induce a tonic depressor effect, also abolished the depressor response suggesting that the reflex abolition was secondary to general activation or disinhibition of the CVLM. Thus, although the CVLM is tonically inhibited by endogenous opioid inputs acting via delta- and kappa-receptors, our data provide no evidence that opioid neurons which provide input to this region constitute a specific and integral component in mediating the aortic depressor response. However, the more general role that opioids play in tonically influencing the resting level of activity in the CVLM, is nevertheless very important in enabling the normal expression of this baroreflex.

Animals↗

PubMed1991

Single-unit and physiological analyses of brain norepinephrine function in behaving animals.

In behaving cats, the single-unit activity of locus coeruleus noradrenergic neurons is strongly activated by a variety of challenges (stressors). For example, exposing cats to a dog or to loud white noise, dramatically increases the activity of these neurons and simultaneously produces strong activation of the sympathetic nervous system. Similarly, glucoregulatory, thermoregulatory, and cardiovascular challenges also coactivate noradrenergic neurons and the sympathetic nervous system. A related research program utilized a simple brainstem response (the monosynaptic jaw closure reflex) to explore the physiological significance of this response of brain noradrenergic neurons. Conditions which activate these neurons were also shown to potentiate the elicited jaw closure-reflex response. Importantly, when the noradrenergic input to the motor side of this reflex pathway was destroyed with a neurotoxin, the conditions which previously potentiated the reflex were now ineffective. These data represent the first demonstration that the release of norepinephrine, at a specific site, and under physiological conditions, facilitates behavioral output in the intact organism.

Action Potentials↗

PubMed1990

Neuropeptide Y-immunoreactive synapses in the intermediolateral cell column of rat and rabbit thoracic spinal cord.

Neuropeptide Y (NPY)-immunoreactive nerve fibers in the intermediolateral cell column of rat spinal cord segments T2-T3 and T8-T10 and rabbit segments T3-T6 were studied with light and electron microscopic immunocytochemistry. Plexuses of NPY-immunoreactive nerve fibers were found by light microscopy. NPY-positive synapses were present electron microscopically but non-immunoreactive synapses greatly outnumbered NPY-immunoreactive ones. In the lateral horn of rat T9, 30% of the vesicle-containing NPY-positive axon profiles formed synapses, 95% of which were axodendritic. These synaptic connections may mediate the effects of brainstem NPY neurons on the activity of sympathetic preganglionic neurons.

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PubMed1990

Cardiovascular effects of opioid antagonist naloxone in rostral ventrolateral medulla of rabbits.

We have examined the influence of endogenous opioids on the basal and reflex control of arterial blood pressure in the pressor region of the rostral ventrolateral medulla (RVLM) of chloralose-anesthetized rabbits. We tested basal effects both in intact animals and after hypotensive hemorrhage. Bilateral administration of the opiod antagonist naloxone (20 nmol, 100 nl) directly into the RVLM induced a gradual and prolonged increase in mean arterial pressure (MAP) (+17 +/- 2 mmHg). This was preceded by a brief and mild depressor effect (-9 +/- 3 mmHg), which was attributable to a transient reduction in excitability immediately after naloxone injection. When naloxone was administered into the RVLM after hemorrhage (20 ml/kg), it improved recovery of MAP relative to saline controls, again producing a gradual, prolonged pressor response (+29 +/- 5 mmHg). The effect of naloxone on a baroreflex in intact animals was only transient, with a brief, nonsignificant attenuation of the reflex depressor response to aortic nerve stimulation. We conclude that endogenous opioids exert a tonic inhibitory influence on RVLM pressor neurons and that this input remains active after hemorrhage. The RVLM may thus be one site for the beneficial effects of naloxone in preventing circulatory decompensation after hemorrhage. In contrast, opioid neurons are not an essential component of baroreflex-mediated sympathoinhibition in the RVLM.

Animals↗

PubMed1990

Single-unit responses of serotonergic neurons to vasoactive drug administration in behaving cats.

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN), heart rate (HR), and arterial blood pressure were recorded in freely moving cats during spontaneous behavior and in response to systemic administration of vasoactive drugs. The activity of serotonergic neurons varied in association with behavioral arousal but was unrelated to spontaneous fluctuations in HR and blood pressure. Bolus administration of phenylephrine hydrochloride and sodium nitroprusside (15-20 micrograms/kg iv) produced a rapid transient increase (35 mmHg) and decrease (49 mmHg), respectively, in mean arterial pressure (MAP). Infusion of phenylephrine and sodium nitroprusside (100 micrograms/ml) produced sustained hypertension (avg MAP 166 mmHg) and hypotension (avg MAP 49 mmHg), respectively. The activity of serotonergic neurons was not significantly altered in response to phenylephrine or sodium nitroprusside administration. Furthermore, no significant changes in unit activity were observed after hydralazine administration (1 mg/kg iv) despite prolonged reflex activation of sympathetic outflow. Thus the activity of DRN serotonergic neurons was unrelated to transient alterations in blood pressure and baroreceptor activity. These results suggest that changes in the activity of serotonergic DRN neurons are not involved in physiological mechanisms underlying reflex alterations in sympathetic (and parasympathetic) outflow invoked by hypertension and hypotension.

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

PubMed1990

Tonic opioid inhibition of the pressor region of the rostral ventrolateral medulla of rabbits is mediated by delta receptors.

From previous observations, we have suggested that an endogenous opioid input tonically inhibits the pressor neurons of the rostral ventrolateral medulla (RVLM) of rabbits. In the present studies, the specific opioid receptor subtype(s) which may be activated by such an endogenous innervation were examined using local administration of selective antagonists. The RVLM pressor region of chloralose-anesthetized and artificially ventilated rabbits was functionally identified by local administration of L-glutamate (5 nmol). Selective blockade of neither mu nor kappa receptors in the RVLM after bilateral injections of beta-funaltrexamine (300-900 pmol) or nor-binaltorphimine (1 nmol), respectively, had any effect on either mean arterial pressure or heart rate. Delta receptors were blocked with ICI 174,864 (30-300 pmol). After the highest dose, there was a significant pressor effect (+32 +/- 6 mm Hg, mean +/- S.E.), which was of immediate onset and rapid time course (approximately 15 min), and which was accompanied by a bradycardia. In contrast, vehicle injections or injection of an inactive analog (ICI 178,173) had no effects. These results, together with previous pharmacological and anatomical evidence, suggest that there exists an enkephalinergic input to the RVLM that tonically inhibits the presympathetic pressor neurons via activation of delta-opioid receptors.

Animals↗

PubMed1989

An enkephalin-containing pathway from nucleus tractus solitarius to the pressor area of the rostral ventrolateral medulla of the rabbit.

A technique combining retrograde tracing of wheat germ-conjugated gold particles with immunocytochemical demonstration of enkephalin-containing neurons was used to study intramedullary enkephalin-containing pathways to the pressor area of the rostral ventrolateral medulla in rabbits. The rostral ventrolateral medulla represents a main source of bulbospinal sympathoexcitatory neurons, and is critical to the tonic and reflex control of blood pressure. Firstly, the distribution of enkephalin-positive neurons and terminal fibres in rabbit medulla were described, with special reference to a moderately dense terminal plexus in the rostral ventrolateral medulla. Then, retrograde tracing studies were conducted; the rostral ventrolateral medullary pressor region was first localized by injection of L-glutamate (25 nmol in 50 nl). Slow (30-min) injections of wheat germ-gold (1.00 microliter) were then made at the same coordinates, resulting in a restricted injection site corresponding to the C1 pressor area, verified by the presence of tyrosine hydroxylase- and neuropeptide Y-containing neurons. Transported gold was revealed by silver reduction, and enkephalin immunoreactive cells were revealed by immunocytochemistry. Enkephalin-positive gold-containing neurons were found primarily in the nucleus tractus solitarius, especially in the commissural and medial intermediate subnuclei. Cells in the nucleus tractus solitarius containing other transmitters (substance P. galanin, neuropeptide Y and catecholamines) did not show the same degree or pattern of double-labelling, suggesting that the transport was not due to non-specific silver reduction or spread from the pipette track. The potential importance of this endogenous intramedullary opiate system is discussed in terms of medullary control of the cardiovascular system. It is hypothesized that this opiate projection from the nucleus tractus solitarius to the rostral ventrolateral medulla could play an important modulatory function, influencing baroreceptor or other cardiopulmonary reflex pathways involved in the primary regulation of the cardiovascular system. Furthermore, this pathway could represent a central substrate underlying opiate effects on the cardiovascular system during such conditions as hemorrhagic shock, stress or opiate intoxication.

Animals↗

PubMed1989

Single-unit responses of serotonergic neurons to glucose and insulin administration in behaving cats.

Extracellular single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN) was recorded in response to glucose loading and insulin administration in conscious, freely moving cats. Serotonergic neurons were identified based on their discharge characteristics, activity across states of behavioral arousal, response to systemic administration of serotonin autoreceptor agonists, and histological localization to the DRN. The spontaneous activity of serotonergic neurons varied in association with behavioral state, reaching their highest level during arousal and their lowest level during rapid-eye-movement sleep, when cells typically stopped firing. The activity of serotonergic DRN neurons was not significantly altered by a glucose load (500 mg/kg iv) that produced an approximately 3.5-fold increase in blood glucose levels. Furthermore, serotonergic DRN neuronal activity was not significantly altered after insulin administration (2-4 IU/kg iv), which lowered blood glucose approximately 50% below control levels, or after the rapid reversal of hypoglycemia by subsequent glucose administration. These results indicate that the activity of serotonergic DRN neurons is unrelated to alterations in blood glucose and is not sensitive to elevations of endogenous circulating insulin levels or to exogenous insulin administration. Furthermore, changes in the activity of serotonergic DRN neurons does not appear to be a component of glucoregulatory mechanisms invoked by either hyper- or hypoglycemia. Overall, these results do not support a role for serotonergic DRN neurons in glucoregulation in the cat.

Animals↗

PubMed1988

Release of substance P in the nucleus tractus solitarius measured by in vivo microdialysis: response to stimulation of the aortic depressor nerves in rabbit.

Substance P (SP) is found in high concentration in the nucleus tractus solitarius (NTS), and is a neurotransmitter candidate in primary baroreceptor afferents to the NTS. Release of SP in the medial NTS of halothane-anesthetized rabbits was measured by in vivo microdialysis. Bilateral electrical stimulation of the aortic depressor nerves (ADN) elicited a significant elevation in SP collected during the period following stimulation, while sham stimulation had no effect. Perfusion through the dialysis probe with a high-potassium (150 mM) solution caused a large increase in the level of SP collected, verifying the neural origin of this release. Possible explanations for the delay in increased release of SP include interaction with carotid afferents, diffusion time, or excitation of SP-containing inputs to the NTS originating elsewhere in the brain. This study demonstrates that SP release in the NTS is elevated by activation of baroreceptor afferents, supporting the hypothesis that SP plays a role in the central integration of cardiovascular control. Whether this release is from primary afferent terminals, or from another source, remains to be seen.

Animals↗

PubMed1987

Effects of physiological manipulations on locus coeruleus neuronal activity in freely moving cats. I. Thermoregulatory challenge.

This and the following two papers examine the activity of locus coeruleus noradrenergic (LC-NE) neurons in response to a variety of physiological manipulations in unanesthetized, unrestrained cats. Unit responses were studied during a constant behavioral state in order to avoid the potentially confounding effects of state changes upon LC-NE unit discharge. In the present study, LC-NE unit activity was recorded during two thermoregulatory challenges: ambient heating and pyrogen-induced fever. These two conditions are particularly interesting since the direction of body temperature change that they produce is the same, but the thermoregulatory responses elicited are opposite, i.e. heat loss and heat gain. LC-NE neurons were activated by both manipulations. In response to ambient heating, neuronal activity increased only with the occurrence of panting, and not during earlier portions of the heating session. Following pyrogen administration, LC-NE neurons responded only during the peak increase in body temperature. Both of these effects on unit activity occurred independent of changes in behavioral state. Since both manipulations similarly increased LC-NE unit activity, despite eliciting opposite thermoregulatory responses, it appears that these neurons do not play a specific role in thermoregulation, but may participate in the response to physiological challenges in general.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1987

Effects of physiological manipulations on locus coeruleus neuronal activity in freely moving cats. II. Cardiovascular challenge.

Several cardiovascular manipulations were examined for their effects on single-unit activity of locus coeruleus noradrenergic (LC-NE) neurons in unanesthetized, unrestrained cats: hydralazine (1 mg/kg, i.v.) was administered to present a tonic hypotensive stimulus, and to activate preferentially the neural component of the sympathoadrenal system; hemorrhage was used to decrease blood volume and to activate both the neural and hormonal components of the sympathoadrenal system; intravenous infusion of isotonic saline was used to increase blood volume. LC-NE neurons were activated by hydralazine, in parallel with the sympathetic response (indicated by elevated heart rate and plasma NE). LC-NE unit activity was decreased following a volume load. However, contrary to previous findings in anesthetized animals, hemorrhage had no effect on LC-NE unit activity, but did activate both components of the sympathetic response. It is concluded that: (1) cardiovascular stimuli can influence the activity of LC-NE neurons, though they show less sensitivity to such stimuli than do primary regulatory mechanisms; (2) the response of LC-NE neurons to physiological stimuli can occur independent of changes in behavioral state; (3) these neurons do not appear to play a specific role in cardiovascular regulation, but may respond to physiological challenges in general; (4) finally, in agreement with previous studies, our data show that LC-NE neurons are generally co-activated with the sympathetic nervous system, but also that the two can be dissociated (e.g. hemorrhage).

Action Potentials↗

PubMed1987

Effects of physiological manipulations on locus coeruleus neuronal activity in freely moving cats. III. Glucoregulatory challenge.

Insulin-induced hypoglycemia and the subsequent administration of glucose were examined for their effects on single unit activity of locus coeruleus noradrenergic (LC-NE) neurons in unanesthetized, unrestrained cats. LC-NE neuronal activity showed an inverse relationship to blood glucose levels. The activity of most cells increased during sustained hypoglycemia, and then decreased following glucose administration. Some neurons were unaffected by hypoglycemia, but were inhibited following glucose. The activation of LC-NE neurons in response to insulin administration generally paralleled the increase in plasma epinephrine, although the adrenal response was more sensitive. These data, together with those reported in the preceding papers, suggest the following general conclusions: (1) physiological stimuli can influence the activity of LC-NE neurons in unanesthetized subjects (although they do so less strongly than environmental stimuli); (2) these effects of physiological stimuli upon LC-NE neurons can be exerted independent of changes in behavioral state; (3) LC-NE neurons do not appear to play a specific role in the regulation of any of the systems examined, but may instead play a more global role in the response to physiological challenges in general; (4) LC-NE neurons are generally co-activated with both the neural and hormonal components of the sympatho-adrenal system, although sympathetic activation can occur in the absence of increased LC-NE activity. A previously hypothesized role for LC-NE neurons in facilitating the behavioral response to environmental stressors may thus be extended to include the response to physiological challenges, and perhaps facilitation of the physiological as well as the behavioral components of the stress response.

Action Potentials↗

PubMed1987

Single-unit responses of serotonergic dorsal raphe nucleus neurons to environmental heating and pyrogen administration in freely moving cats.

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was examined in response to environmental heating and pyrogen-induced fever in freely moving cats. In the heating study, ambient temperature was rapidly raised from a baseline of 25 degrees to 43 +/- 1 degrees C and maintained at this level for 2 h. Cats displayed hyperthermia, intense panting, and signs of heat stress, however, the discharge rate of serotonergic neurons of the dorsal raphe nucleus was not significantly different from baseline at any time during heat exposure. Similarly, the activity of these neurons was not significantly altered at any time during an approximately 6-h long febrile response induced by the synthetic pyrogen muramyl dipeptide (50 micrograms/kg, i.v.). These results indicate that serotonergic unit activity in the dorsal raphe nucleus is not related to either the activation of behavioral or physiological mechanisms underlying heat defense, or to alterations in thermoregulatory mechanisms during the febrile response to exogenous pyrogen. Furthermore, because these neurons do not respond to an elevation in body temperature induced by either ambient heating or pyrogen, they do not appear to be directly temperature-sensitive. These results do not support a specific role for serotonergic neurons of the dorsal raphe nucleus in thermoregulation.

Animals↗

PubMed1986

Single unit activity of noradrenergic neurons in locus coeruleus and serotonergic neurons in the nucleus raphe dorsalis of freely moving cats in relation to the cardiac cycle.

Single unit activity of serotonergic (5-HT) neurons in the nucleus raphe dorsalis (NRD) and of noradrenergic (NE) neurons in the locus coeruleus (LC) was recorded in relation to the cardiac cycle in awake, freely moving cats. The discharge of NRD-5-HT neurons showed no relationship to the cardiac cycle, while LC-NE neurons displayed a cardiac periodicity such that the units were most likely to fire from 80 to 180 ms after the peak of the cardiac r-wave (diastole), and least likely to fire during the period from 40 ms before to 60 ms after the r-wave (systole). The strength of this periodicity was inversely related to the discharge rate of individual cells. Exposure to a noxious environmental stimulus (15 min of 100 dB white noise) greatly attenuated the cardiac relationship of LC-NE neurons. A blood volume expansion of approximately 15% (9.0 ml/kg b. wt.) decreased unit rate by about 25%, but did not alter either the timing or the magnitude of the LC-NE cardiac relationship. These data are discussed in terms of the participation of NRD-5-HT and LC-NE neurons in cardiovascular function, and the possible role of LC-NE neurons in short- and long-term volume homeostasis.

Action Potentials↗

PubMed1986

Single unit activity of locus coeruleus neurons in the freely moving cat. I. During naturalistic behaviors and in response to simple and complex stimuli.

The single unit activity of presumed noradrenergic (NE) neurons in the area of the locus coeruleus (LC) was recorded in freely moving cats. Consistent with previous reports, the activity of LC neurons was found to be state dependent: active waking greater than quiet waking greater than slow wave sleep greater than REM sleep (virtually silent). The activity of these neurons showed no relationship to movement per se. In response to simple sensory stimulation, LC units showed a short latency, short duration excitatory response. In response to a variety of non-noxious naturalistic stimuli, e.g. rats, food and a conspecific, LC unit activity did not increase above an active waking baseline. However, in response to noxious stimuli, e.g. pinches, visual threats, emesis, and forced treadmill running, LC unit activity increased above that during active waking and reached its highest levels. These data, in conjunction with those in the following report, are consistent with a general role for NE-LC neurons in the organism's adaptive response to environmental and physiological challenges.

Action Potentials↗

PubMed1985

Noradrenergic modulation of sensorimotor processes in intact rats: the masseteric reflex as a model system.

The masseteric jaw closure reflex was utilized as a model system with which to gauge the functional activity of central noradrenergic neurons. This system was chosen because it is a simple monosynaptic reflex the neuronal substrate of which receives a dense noradrenergic input. The modulatory effects of norepinephrine (NE) on this response in the intact, chloral hydrate-anesthetized rat were studied with a variety of pharmacological strategies. Initially, a reflex facilitation was obtained with the catecholamine precursor L-DOPA. Manipulations with greater specificity of action on the noradrenergic system were then employed. First, we used the presynaptic alpha-2 noradrenergic agonist clonidine, which acts to decrease noradrenergic transmission. Clonidine attenuated the amplitude of the reflex, and this suppression was blocked by pretreatment with the alpha-2 antagonist yohimbine. The effects of yohimbine itself were then examined, and a biphasic effect was obtained. At low doses, at which it preferentially acts as an antagonist at presynaptic alpha-2 receptors and increases noradrenergic transmission, yohimbine enhanced the reflex. At higher doses, at which it also displays postsynaptic alpha-1 antagonist activity, yohimbine depressed the reflex. This reflex modulation by yohimbine was blocked by pretreatment with the alpha-1 antagonist prazosin. The anatomical site of the observed effect was then localized to the direct noradrenergic innervation of the reflex circuitry by locally destroying, with 6-hydroxydopamine, the noradrenergic terminals in the trigeminal motor nucleus mediating the response. This significantly attenuated the reflex modulation by yohimbine, without affecting elicitation of the reflex itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗