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PubMed1988

The effects of intraventricular carbachol injections on the free-running activity rhythm of the hamster.

The effects of light on the circadian pacemaker in the suprachiasmatic nucleus (SCN) are mediated by the retinohypothalamic tract (RHT) and by the retinogeniculosuprachiasmatic tract (RGST). The neurotransmitter of the RGST is neuropeptide Y. The RHT may contain glutamate and aspartate. Recent evidence indicates that acetylcholine could also be involved in phase shifting by light. We determined that intraventricular injections with an acetylcholine agonist, carbachol, induces phase advances during the subjective day and phase delays during the early subjective night. No differences were observed between phase shifts induced in constant darkness and those induced in continuous light. A dose-response curve for carbachol was described at circadian time 6 (CT6). Injections at CT14 with various dosages of carbachol indicated the same dose dependency for this circadian time. Finally, carbachol injections in split animals resulted in similar responses of the two components of the split activity rhythm.

Animals↗

PubMed1983

Studies of somatostatin-induced barrel rotation in rats.

Somatostatin (SRIF) has been reported to induce abnormalities of motor behavior in rats when injected intraventricularly. Following an injection, non-lesioned rats develop unilateral extension of the limbs, a twist about the long axis, and repeated lateral rolling, called "barrel rotation". It has not been clear whether this behavior is due to a pharmacologic action of SRIF, such as an effect of SRIF on systems of motor control. Prior reports observed the response only at high doses of SRIF, and found no dose-response relationship for it. We have investigated whether this response is due to a pharmacologic effect of SRIF. We have also studied where SRIF acts, when injected intraventricularly, to induce this response. We have found that SRIF-induced rotation increases linearly with doses up to 10 micrograms and thereafter declines. Biologically inactive analogues of SRIF did not induce barrel rotation. Dose-response studies of intraventricular and intracerebral microinjections indicated that SRIF acts at the vestibular nuclear complex (VNC) to induce rotation. At VNC, 0.25 micrograms SRIF produced postural abnormalities. We conclude that barrel rotation is due to a pharmacologic action of SRIF, and that SRIF does act upon a system of motor control, the VNC, to induce this response.

Animals↗

PubMed1998

[Role of rostral ventrolateral medulla in the pressor response to intraventricular (4th) injection of substance P].

Experiments were done in rabbits anaesthetized with urethane and immobilized under artificial respiration. It was found that substance P (SP, 0.8 ng/kg dissolved in 100 microliters artificial cerebro-spinal fluid, CSF) injected into the 4th ventricle induced either a rise or a drop of pulmonary arterial pressure (PAP) with predominated pressor response. In addition, a rise in carotid arterial pressure (CAP) and reduction in heart rate (HR) were also observed, whereas no significant alteration in PAP, CAP and HR was observed. Microinjection of SP receptor antagonist [D-Pro2, D-Phe7, D-Trp9]--SP (5-10 ng dissolved in 0.5 microliter CSF) or phentolamine (2-3 micrograms dissolved in 0.5 microliter CSF) into the bilateral rostral ventrolateral medulla (rVLM) prior to intraventricular injection of SP could block the SP-induced pressor responses in pulmonary and carotid arteries, while microinjection of SP receptor antagonist or phentolamine into bilateral caudal ventrolateral medulla (cVLM) at the same dosage had no effect. The results show that SP-induced pulmonary and carotid pressor responses may be mediated through SP-receptor and alpha-adrenergic receptors in the rostral ventro-lateral medulla (rVLM).

Animals↗

PubMed1978

Synaptic structures and quantification of catecholaminergic axons in the nucleus tractus solitarius of the rat: possible modulatory roles of catecholamines in baroreceptor reflexes.

The synaptic organization in the nucleus tractus solitarius (NTS) of the rat at the level of the obex was examined by fluorescence and electron microscopy in 5 groups of animals: (1) normal control, (2) intraventricular injection of 5-OHDA, (3) intraventricular injection of 6-OHDA, (4) intracranial denervation of the IXth and Xth cranial nerves, and (5) intraventricular injection of 5-OHDA 48 h after intracranial denervation of the IXth and Xth cranial nerves. A dense network of catecholaminergic nerves was observed in the NTS and several catecholaminergic neurons were seen to be scattered in the lateral portion of the NTS. Nerve cells in the NTS were small in size (15-20 micrometer in diameter). In addition to ordinary axodendritic and axo-somatic synapses, serial synapses were occasionally encountered. The first presynaptic site in some of the serial synapses was identified as catecholaminergic by 6-OHDA treatment. After treatment with 5-OHDA, 2.4% of axon varicosities were identified as catecholaminergic by small dense-cored vesicles. After administration of 6-OHDA, 5.19% of dense degenerated axon varicosities were counted. After intracranial deafferentation of the IXth and Xth cranial nerves, 5.3% of dense degenerated axon varicosities were found. The total number of axon varicosities in 6800 sq.mum area was decreased by 9% after the injection of 6-OHDA and 11% after deafferentation of the IXth and Xth cranial nerves. At least 3 types of axons could be identified: (1) catecholaminergic axons with small dense-cored vesicles after 5-OHDA administration, (2) afferent axons from the IXth and Xth cranial nerves with small clear vesicles, and (3) axons with small clear vesicles probably originated from the supramedullary nucleus. The results of the present study suggest that catecholamines modulate reflex blood pressure regulation within the NTS of the rat.

Animals↗

PubMed1987

Intrathecal administration of netilmicin in gentamicin-resistant ventriculitis.

In ventriculitis caused by Gentamicin-resistant staphylococcus aureus and staphylococcus epidermidis, Netilmicin was administered intrathecally to 19 patients under continuous control of the Netilmicin concentration in cerebro-spinal fluid (CSF). This therapy was able to bring these otherwise lethal infections under control, usually within 10 days. Pharmacokinetic studies with different doses have shown that doses of 2 X 3 mg are to be recommended in moderately severe cases of ventriculitis, and in most severe infections 3 X 3 mg daily intraventricularly for adults. In infants daily intraventricular injections of 2 X 0.4-0.5 mg Netilmicin are a sufficient dose to produce an effective antibiotic concentration level.

Adolescent↗

PubMed1982

Central nervous system effect of calcitonin: stimulation of prolactin release in rats.

Effect of [Asu 1,7]eel calcitonin (CT) on prolactin (PRL) release was examined in male rats under urethane anesthesia. Intravenous injection of 4-20 micrograms [Asu1,7]eel CT did not modify plasma PRL levels. Injections of 0.5-2.5 micrograms [Asu1,7]eel CT into the lateral ventricle produce a significant and dose-related increase of plasma PRL within 10 min of injection. When intraventricularly injected in an equimolar dose (0.74 nmol/10 microliters), eel CT11-32, eel CT15-32, [Asu1,7]eel CT1-16 and [Asu1,7]eel CT1-9 showed 44.8, 25.7, 19.9 and 10.1% the potencies of [Asu1,7]eel CT, respectively, in stimulating activity of PRL release. The rise of plasma PRL after [Asu1,7]eel CT injection were significantly less or abolished not only in hypothalamic-lesioned rats but also in rats with complete deafferentation. Pretreatment with alpha-methyl-p-tyrosine (250 mg/kg, 12 h before) but not with p-chlorophenylalanine (300 mg/kg, 72 and 24 h before) resulted in a suppression of [Asu1,7]eel CT-induced PRL release. These results suggest the following: first, PRL release is stimulated by centrally injected [Asu1,7]eel CT, the action site of which may exist in the extrahypothalamic area; second, brain catecholamines may be involved in the mechanism of [Asu1,7]eel CT-evoked PRL release; third, the C-terminal portion of the peptide may play an important role in stimulating PRL release.

Animals↗

PubMed1999

Effects of orphanin FQ on endomorphin-1 induced analgesia.

Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the mu-opiate receptor. In the present study, the effect of OFQ or/and endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i.c.v.) administration of OFQ (1, 5 microg) could shorten tail-flick latency; In contrast, intrathecal (i.t.) administration of OFQ (1, 2 or 10 microg) could increase the latency; i.c.v. (1, 2, 5 microg) or i.t. (0.2, 2, 5 microg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5 microg) when intraventricularly injected together with endomorphin-1 (5 microg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1 microg) intrathecally injected together with endomorphin-1 (0.2 microg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested.

Analgesics, Opioid↗

PubMed1982

Stimulation by serotonin of vasoactive intestinal polypeptide release into rat hypophysial portal blood.

The effect of serotonin (5-HT) on plasma vasoactive intestinal polypeptide (VIP) levels in hypophysial portal blood was studied in urethane-anesthetized rats. Portal blood was collected by the parapharyngeal approach and plasma VIP was determined by radioimmunoassay. Mean (+/- SE) basal plasma VIP level was 1799 +/- 232 pg/ml, which was slightly decreased during the control experiments in which physiological saline was injected either intraventricularly or intravenously. Intraventricular injection of 5-HT (2 and 10 micrograms/rat) resulted in a significant increase in plasma VIP concentrations within 20 min. Intravenous injection of L-5-hydroxytryptophan (5-HTP, 1 mg/100 g BW), a precursor of 5-HT, also caused an increase in VIP concentrations in hypophysial portal plasma. The flow rate of hypophysial portal blood did not change throughout the experiments. These findings suggest that 5-HT stimulates VIP release from the median eminence into the hypophysial portal vessels in the rat.

Animals↗

PubMed1971

Antinociceptive activity of morphine after injection of biogenic amines in the cerebral ventricles of the conscious rat.

1. A simple cannula and a cannula guide for making injections into the cerebral ventricles of conscious rats are described.2. Intraventricular injections of 5-hydroxytryptamine (5-HT) or of noradrenaline (NA) were without effect on the nociceptive threshold of rats.3. Intraventricular injection of 5-HT potentiated the antinociceptive effect of morphine. Reserpine pretreatment antagonized the antinociceptive effect of morphine; this effect was reversed by intraventricular injection of 5-HT.4. Intraventricular injection of NA attenuated the antinociceptive action of morphine but was without effect on the inhibition by reserpine of the antinociceptive effect of morphine.5. Subcutaneous injection or slow intravenous infusion of either 5-HT or NA (up to 300 mug/rat) were without significant effect on the antinociceptive effects of morphine.6. Intraperitoneal administration of dopa increased the nociceptive threshold above normal, but reduced the antinociceptive effect of morphine. Intraventricular injection of either dopa or dopamine had no antinociceptive effect but inhibited that of morphine.7. It is suggested that the antinociceptive effect of morphine may depend on the balance between the concentrations of 5-HT and NA in the brain.

Animals↗

PubMed1990

The role of neuropeptide Y (NPY) in control of gonadotropin and prolactin release in the rat.

Neuropeptide Y is a peptide found in a variety of hypothalamic loci which is frequently colocalized with catecholamines. It is also secreted into hypophyseal portal vessels. We have previously evaluated the effects of this peptide on FSH, LH and prolactin release. In ovariectomized females neuropeptide Y inhibits LH release. It has similarly been reported to inhibit LH release in intact males; however, estrogen priming of ovariectomized animals converts this inhibitory action into a stimulatory effect. In ovariectomized animals the peptide has a direct stimulatory effect on perifused pituitary cells, enhancing the release of both FSH and LH, an effect which is contrary to that obtained with LH release after intraventricular injection of the peptide. In the present experiments the physiological significance of these effects has been evaluated by the intraventricular injection (3V) of highly specific antiserum directed against the peptide. In ovariectomized and in ovariectomized, estrogen-primed rats, the third ventricular injection of antiserum had no effect on gonadotropin release. In male rats intraventricular injection of the antiserum elevated LH, which indicates that the inhibitory action of the peptide seen in intact males is of physiological significance. However, it has been reported by others that the proestrous type discharge of LH-RH is blocked by intraventricular injection of neuropeptide Y antiserum. Neuropeptide Y might therefore play an essential role in the preovulatory release of LH. On the other hand, others have shown that intraventricular injection of neuropeptide Y in male rats can either stimulate, at low doses, or inhibit, at high doses, the release of prolactin. We have confirmed the inhibitory action, which appears to be of physiological significance since antisera directed against the peptide injected intraventricularly resulted in an elevation of prolactin release. The results of these studies indicate that neuropeptide Y plays a very important and often physiologically significant role in the control of LH and prolactin release by hypothalamic action.

Animals↗

PubMed2002

Sodium deficiency enhances the behavioral responses to centrally administered vasopressin in rats.

The ability of sodium deficiency to stimulate vasopressin (VP) release was examined by determining if sodium deficiency sensitizes the animal to the behavioral disruption caused by intraventricular injections of VP. In sodium-replete rats, intraventricular injections of 50 ng VP on Day 1 had no effect on behavior, but this dose elicited abnormal behaviors (barrel rolls, hind-limb extensions) when administered on Day 2, indicating a sensitization phenomenon. In separate experiments, the first intraventricular injection of 50 ng VP in sodium-deficient but not in sodium-replete rats also elicited barrel rotations followed by hind-limb extension. Intraventricular injection of VP also disrupted motor behavior in sodium-replete rats that had multiple prior experiences with sodium deficiency but not in naive rats. These results show that sodium deficiency can mimic the effect of central injections of VP in sensitizing the brain to the behavioral effects of exogenous VP. This suggests that sodium deficiency induces the central release of VP.

Animals↗

PubMed1988

Angiotensin II, bombesin and naloxone in tooth pulp and cutaneous nociceptive mechanisms in rabbits.

The effects of angiotensin II (A II), bombesin (B) and naloxone (N) on the amplitude of the late component of the evoked potentials of the cortex (EP) were studied by electrocutaneous (ECS) and tooth pulp (ETS) stimulation. An intraventricular (50 ng/kg) or intravenous (5 micrograms/kg) injections decreased the amplitude of the negative-positive component with a 20-40 ms latency (NP20-40) EP to ETS, but not to ECS. Saralasin (A II antagonist) injected intraventricularly (130 ng/kg) abolished this effect of A II in response to ETS. N intraventricular injections (30 micrograms/kg) increased the amplitude of NP20-40 EP to ETS, but not to ECS. B (intraventricular injection 20 ng/kg decreased the amplitude of NP20-40 EP to ECS, but not to ETS. This suggests there are the specific mechanisms in analgesia induced by A II and B in the pathways activated by ECS and ETS.

Angiotensin II↗

PubMed1966

Analysis of some central actions of nicotine injected into the cerebral ventricles of cats.

1. In unanaesthetized cats intraventricular injections of 2.5-10 mug nicotine produced blinking, narrowing of the palpebral fissures, retching, vomiting and asynchronous twitching of the ears. With larger doses (30-100 mug) the ear twitching was interrupted for a short time by laying back of the ears. Respiration first became laboured and deep, then rapid and shallow following which panting occurred. There was salivation, loud calling, micturition and defaecation. With still larger doses (300-1000 mug) there was torticollis, ataxia and blind charging sometimes followed by a clonic-tonic convulsion.2. In cats anaesthetized with chloralose only some of these effects followed the intraventricular injection of nicotine, i.e. the ear response, respiratory changes and salivation. In addition, the pinna reflex was facilitated.3. The ear response and the facilitation of the pinna reflex did not occur on perfusion of nicotine from a lateral ventricle to aqueduct. They result from an action on superficial structures in the cervical cord between C1 and C2. Applied to this region of the cord, nicotine produced the ear response within 10-60 sec, sometimes in concentrations as low as 1/100,000. Applied below C2, nicotine was ineffective.4. Transecting the cord below C2 or cutting the dorsal and ventral roots of C1, C2 and C3 bilaterally did not affect the ear response produced by topical application or by intraventricular injection of nicotine. Transection of the cord above C1 abolished it.5. Hexamethonium applied to the cervical cord between C1 and C2 inhibited the ear response and the facilitation of the pinna reflex whether produced by nicotine applied topically or injected intraventricularly.6. The salivation and the respiratory changes produced by intraventricular injections of nicotine did not occur when nicotine was perfused from a lateral ventricle to the aqueduct. They result from an action of the nicotine on structures situated superficially in the brain stem. Nicotine had no sialogogue or respiratory effect when applied to the region of the cord at which it produced an ear response, but perfused through the subarachnoid space from interpeduncular fossa to cisterna magna or injected into the subarachnoid space alongside the brain stem, it produced these effects.7. Hexamethonium perfused from interpeduncular fossa to cisterna magna inhibited the salivary secretion as well as the respiratory changes produced by nicotine similarly applied.8. The efferent pathway for the salivation is parasympathetic since it no longer occurred after cutting the chorda-lingual nerve or after intravenous atropine.9. Intravenous injections of nicotine also produced the ear response with facilitation of the pinna reflex, salivation and hyperventilation in the anaesthetized cat, but only the ear response and facilitation of the pinna reflex are central effects. The salivation and hyperventilation following intravenous injection are due to peripheral actions of nicotine.

Journal Article↗

PubMed1990

Tolerance to nicotine-induced sympathoadrenal stimulation and cross-tolerance to stress: differential central and peripheral mechanisms in rats.

Nicotine stimulates the secretion of catecholamines from sympathetic nerve endings and adrenal medulla by acting on peripheral nicotinic cholinergic receptors. Nicotine is also a potent stimulant in the central nervous system but the significance of nicotinic receptors in brain in mediating cardiovascular and sympathoadrenal responses to nicotine is unclear. The responses of resting plasma catecholamines, blood pressure and heart rate were compared in rats receiving nicotine, administered either systemically or intracerebroventricularly (i.c.v.). Sympathoadrenal stress responses were also studied in rats rendered tolerant to nicotine from repeated systemic or intraventricular injections. Nicotine, given either intraventricularly or systemically, produced dose-related increases in the concentration of epinephrine in plasma. Little effect on norepinephrine in plasma was observed with nicotine given intraventricularly, indicating predominant stimulation of adrenomedullary pathways. In contrast, nicotine, given systemically, produced comparable increases in both epinephrine and norepinephrine. Blood pressure increased and heart rate fell in response to either intraventricular or systemic administration of nicotine. Rats exhibited tolerance to nicotine 24 hr after a single intraventricular injection; however, tolerance was not detected with systemically injected nicotine unless the injections were given at least every 30 min. Whereas rats rendered tolerant to systemic administration of nicotine were cross-tolerant to stress, with respect to sympathoadrenal stimulation, cross-tolerance with stress was not detected in rats treated with nicotine repeatedly by the intraventricular route. These results indicate that nicotinic receptors in brain modulate the central sympathetic outflow and adapt readily to nicotine stimulation with prolonged tolerance, but are probably not involved in sympathoadrenal stress responses. Peripheral nicotinic receptors, regulating sympathoadrenal secretion of catecholamines, displayed much shorter-lasting tolerance.

Adrenal Medulla↗

PubMed1975

Cholinergic mechanisms in central thermoregulation in pigeons.

1. In unanaesthetized pigeons the effect on cloacal temperature was studied of acetylcholine (ACh), carbachol, atropine and (+)-tubocurarine injected into a cannulated lateral cerebral ventricle. The experiments were carried out at an ambient temperature of 19-25 degrees C. 2. ACh or carbachol injected intraventricularly produced hyperthermia, and in larger doses hyperthermia followed by hypothermia. These were central effects because they were not obtained when these drugs were injected in the same doses intravenously. 3. Atropine injected intraventricularly produced hypothermia which was greater and longer lasting than the hypothermia produced with the same dose of atropine injected intravenously. After the intraventricular injection of atropine the hyperthermic effects of ACh and of carbachol were abolished. 4. (+)-Tubocurarine injected intraventricularly produced a long-lasting hyperthermia in doses which had no effect on temperature when injected intravenously. After the intraventricular injection of tubocurarine the hypothermic effects of ACh and of carbachol were abolished. 5. It is concluded that the effects of ACh had carbachol imitate the effects of ACh released from cholinergic neurones in the central pathway involved in temperature regulation. The hypothermic effect of atropine is attributed to unmasking the activity of continuously released ACh acting on nicotinic receptors, and the hyperthermic effect of tubocurarine to unmasking the activity of continuously released ACh acting on muscarinic receptors.

Animals↗

PubMed1989

Morphologic alterations in rat brain following systemic and intraventricular methotrexate injection: light and electron microscopic studies.

To determine the morphological substrate of acute methotrexate (MTX) encephalopathy, light and electron microscopic studies were performed on rat brains after short-term intraperitoneal (IP) and intraventricular (IV) injections of MTX. In both models, Alzheimer type II astrocytosis was the initial and major pathologic alteration seen by light microscopy. The neurons, oligodendrocytes, myelin and endothelial cells were relatively spared. Ultrastructural studies showed pleomorphism and condensation of mitochondria, membrane-bound vacuoles, prominent stacks of sparsely granular, rough endoplasmic reticulum and progressive hydropic swelling of astrocytic perikarya and their processes. The astroglial alterations were reversible after cessation of the drug but persisted for a longer time with repeated IP administration. Gastrointestinal complications and overall mortality were also greater with higher doses and increasing frequency of IP MTX injection. White matter necrosis was noted only after IV injection of high-dose MTX. The neuropathologic changes of MTX leukoencephalopathy can be replicated in an animal model by IV injection of the drug. The reversibility of the changes that were seen following IP administration correlates with the transient neurologic deficits observed in some patients after high-dose systemic MTX therapy. The initially selective astroglial effect suggests that astrocytes might be a target for MTX toxicity, although other central nervous system components may also be adversely affected by the drug.

Alzheimer Disease↗

PubMed1981

Stimulation by bombesin of immunoreactive somatostatin release into rat hypophysial portal blood.

Bombesin was injected into the cerebral ventricle of male rats anesthetized with urethane to study its effect on plasma levels of immunoreactive somatostatin (IRS) in hypophysial portal and jugular blood. An intraventricular injection of bombesin (0.2 and 2 micrograms/rat) caused a significant and dose-related increase in plasma IRS in hypophysial portal blood but not in jugular blood. Although bombesin placed into the cerebral ventricle is known to stimulate glucagon and epinephrine release, an iv injection of glucagon (100 micrograms/100 g BW) or epinephrine (2.5 micrograms/100 g BW) did not cause any significant changes in plasma IRS levels in hypophysial portal and jugular blood, suggesting that these substances do not mediate bombesin stimulation of portal IRS release. Pretreatment with naloxone (75 micrograms/100 g BW, iv) failed to affect the portal IRS release induced by bombesin (2 micrograms/rat), indicating that the opiate receptor is not likely to be involved in this reaction. To ascertain whether IRS released by bombesin into hypophysial portal blood is biologically active, the effect of bombesin on the plasma GH level was then examined. Bombesin (2 micrograms/rat) injected intraventricularly completely suppressed the rise of plasma GH after the intraventricular injection of beta-endorphin (1 microgram/rat) or the iv injection of prostaglandin E1 (5 micrograms/100 g BW). Bombesin thus appears to stimulate the secretion of IRS, and probably biologically active somatostatin as well, from the hypothalamus into hypophysial portal blood, thereby inhibiting GH release from the anterior pituitary.

Animals↗

PubMed1988

[Anticonvulsant properties of the cerebrospinal fluid during activation of the antiepileptic system of the brain].

Cerebrospinal fluid (CSF) was obtained after 30-40 sessions of daily electrical stimulation of the cat cerebellum vermis. The intraventricular injection of CSF (10 microliters) to Wistar rats increased the latent period of initial seizure manifestations, significantly reduced the number of animals with seizures and reduced the severity of seizures induced by korazol injection (40 mg/kg). Analogous seizure changes were observed in rats after intraventricular injection of CSF (10 microliters) from cats subject to 3-10 electroshock seizure fits. Intraventricular injection of CSF (250 microliters) obtained from cats after electroshock to cats with strychnine-induced epileptic foci in the brain cortex led to the suppression of the epileptic activity. The conclusion was made that different ways of antiepileptic system activation cause the accumulation of endogenous antiepileptic substances in CSF.

Animals↗