Intraseptal Injection Research Articles

Neurohypophyseal hormone receptors in the septum are implicated in social recognition in the rat

The effects on social recognition memory of (Arg(8))-vasopressin (AVP-(1-9), [pGlu(4), Cyt(6)]AVP-(4-8) and oxytocin locally administered into the rat's septum were investigated. In the behavioural paradigm used, a juvenile intruder was presented to an adult resident male rat twice for 5 min, with an inter-exposure interval of 120 min. Peptide-free residents investigated the juvenile during the second encounter as long as during the first encounter. Intraseptal injection just after the first encounter with graded doses of (Arg(8))-vasopressin, [pGlu(4),Cyt(6)]AVP-(4-8) or oxytocin caused a decrease of social investigation, as compared to placebo treatment, indicating facilitation of social recognition. The least effective dose was 100pg, 200pg and 300pg respectively. The action of vasopressin was blocked by both d(CH(2))(5)[Tyr(Me)(2)]AVP and d(CH(2))(5)[D-Ile(2)Ile(4)]AVP, V(1) and V(2) vasopressinergic receptor antagonists, but not by desGly(NH(2))(9)-d(CH(2))(5)[Tyr(Me)(2)Thr(4)]-OVT, an oxytocinergic receptor antagonist. None of the antagonists blocked the oxytocin-facilitating action on social recognition. They also did not affect social recognition when injected alone. The effects of vasopressin seem to be mediated by vasopressinergic receptors dissimilar to those found in the periphery, while the receptors involved in the action of oxytocin remain to be elucidated.

Chlordiazepoxide-induced working memory impairments: Site specificity and reversal by flumazenil (R015-1788)

The following studies examined the dose and time dependence, site specificity, and reversibility of chlordiazepoxide (CDP)-induced working memory impairments in adult male Sprague-Dawley rats. The rats were tested in a delayed non-match-to-sample radial-arm maze task in which a 1-h delay was imposed between the first four (predelay) and all subsequent (postdelay) arm choices. Intraperitoneal (ip) injection of 2.5 or 5.0 but not 1.25 mg/kg CDP immediately following the predelay session impaired performance in the task. CDP increased the number of errors and decreased the number of correct choices during the postdelay session. The observed working memory impairments also appeared to be site specific since injection of CDP into the medial septum, but not into the anterior amygdala nuclei, immediately following the predelay session also impaired working memory in a dose-related manner. Furthermore, there was a time window for CDP-induced working memory impairments since intraseptal injection of the drug immediately but not 15 min following the predelay session disrupted memory. This observation suggests that the performance deficits reflect disrupted working memory and not proactive effects on performance or the induction of state-dependent learning. In the final experiment, rats were injected ip with either saline or an amnestic dose of CDP (5.0 mg/kg) following the predelay session and then were immediately infused with 10 nmol flumazenil (RO15-1788), a benzodiazepine receptor antagonist or vehicle, into either the medial septum or anterior nuclei of the amygdala. Intraseptal injection of flumazenil prevented the working memory impairments produced by ip injection of CDP. In contrast, intra-amygdala injection of flumazenil did not attenuate, enhance, or modify the CDP-induced working memory impairment. These observations suggest that CDP disrupts working memory by interacting with benzodiazepine receptors in the medial septum.

Effects of intra-septal injection of naloxone on hippocampal acetylcholine release in freely moving rats

Effects of intra-septal injection of naloxone on hippocampal acetylcholine release in freely moving rats

Increases in the local cerebral blood flow (LCBF) in the hippocampus (HPC) by intra-septal injection of naloxone (NAL) in the rat

Increases in the local cerebral blood flow (LCBF) in the hippocampus (HPC) by intra-septal injection of naloxone (NAL) in the rat

Septal α-noradrenergic antagonism in vivo blocks the testing-induced activation of septo-hippocampal cholinergic neurones and produces a concomitant deficit in working memory performance of mice

In order to test the hypothesis that alpha-noradrenergic receptors in the septum 1) play an important functional role in the mediation of trans-synaptic control of the neurones of the cholinergic septo-hippocampal pathway and 2) produce resultant modulation of working memory performance, we have investigated the effects in vivo of the acute intraseptal injection of an alpha-antagonist, phenoxybenzamine, in mice. Neurochemical analysis was performed using measures of the kinetics of sodium-dependent high-affinity choline uptake in samples of hippocampus from injected mice and their relevant controls in both quiet conditions and immediately following selective working memory testing in an 8-arm radial maze. Results show that whereas the injection of phenoxybenzamine produces no significant alteration of the activity of the cholinergic septo-hippocampal neurones in quiet conditions, the pretrial (20 min) administration of this drug almost totally abolished the usually observed increase in hippocampal cholinergic activity induced by testing. This inhibition of cholinergic activation was associated with a parallel working memory deficit. The results provide further direct support for the hypothesis that septal noradrenergic afferents via alpha-receptors mediate a phasic and net excitatory trans-synaptic influence on the cholinergic septo-hippocampal pathway during working memory testing and thereby significantly contribute to the modulation of the level of working memory performance.

Effect of intraseptal injection of fasciculin upon memory of two aversive tasks in rats: J. A. Qillfeldt, 1B. Bolioli, 2C. Dalmaz, 1C. Huang, 1M. B. Ferreira, 1M. E. Pereira, 1F. Schneider, 1C. A. Netto, 1 and I. Izquierdo1 ( 1Center of Memory, Dept. of Biochemistry and Dept. of Morphological Sciences, Institute of Biosciences, UFRGS, Porto Alegre RS, Brasil; and 2Neurochemistry

Effect of intraseptal injection of fasciculin upon memory of two aversive tasks in rats: J. A. Qillfeldt, 1B. Bolioli, 2C. Dalmaz, 1C. Huang, 1M. B. Ferreira, 1M. E. Pereira, 1F. Schneider, 1C. A. Netto, 1 and I. Izquierdo1 ( 1Center of Memory, Dept. of Biochemistry and Dept. of Morphological Sciences, Institute of Biosciences, UFRGS, Porto Alegre RS, Brasil; and 2Neurochemistry

Septo-hippocampal and cortical cholinergic activation during the acquisition, reversal and extinction of a reference memory task in a radial maze by C57BL/6 mice

It has been shown in numerous studies that memory testing can alter presynaptic cholinergic activity within the hippocampus. In the present experiments, the role of the noradrenergic input to the septal cholinergic neurons in the immediate increase in cholinergic activity induced by the first training session of a spatial reference memory task in an 8-arm radial maze was investigated. The effects of bilateral intraseptal injections of noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake (SDHACU) were studied in ‘resting’ animals (basal level) or in ‘trained’ animals injected 20 min before training and sacrificed immediately after the test. The results showed that: (1) the injection of maprotiline, a noradrenaline 3euptake inhibitor (0.06 ng/site), induced an increase in hippocampal SDHACU in ‘resting’ animals, whereas the α2-adrenoceptor agonist UK 14304 (1.5 ng) significantly reduced the basal level of SDHACU; (2) none of the α-adrenoceptor antagonists used (phenoxybenzamine, 10 and 100 ng; BE 2254, 100 and 500 ng; yohimbine, 0.5 and 50 ng) significantly affected the basal level of hippocampal SDHACU, and only the α1-adrenoceptor antagonist BE 2254 (500 ng) significantly reduced the testing-induced activation of SDHACU. Taken together, these findings suggest that noradrenaline may exert a bimodal regulatory influence on the activity of septo-hippocampal cholinergic neurons. The behavior-induced activation of hippocampal SDHACU could be partly mediated by the stimulation of α1-adrenoceptors, whereas postsynaptic α2-adrenoceptors may be important for the maintenance of a tonic inhibition of the steady-state cholinergic activity in the hippocampus. These results are further evidence for a regulatory noradrenergic influence on the activity of septal cholinergic neurons.

Hippocampal rhythmical slow activity following ibotenic acid lesions of the septal region. I. Relations to behavior and effects of atropine and urethane

The effects of intraseptal injections of various concentrations of ibotenic acid on hippocampal electrical activity were studied in freely moving and urethane-anesthetized rats. Ibotenic acid selectively abolished the atropine-sensitive form of hippocampal rhythmical slow activity (RSA) normally seen during urethane anesthesia. Large amplitude irregular activity (LIA) and RSA in the waking state were somewhat depressed as well. Despite this, clear RSA persisted in the waking state in association with locomotion or struggling (Type 1 behavior). As in normal rats, such RSA was resistant to systemic administration of atropine. Analysis of brain sections stained with gallocyanin or for acetylcholinesterase showed that ibotenic acid produced cell loss in the dorsal lateral septal nucleus and the septohippocampal nucleus. Cells in the medial septal and diagonal band nuclei were resistant to ibotenic acid. The results suggest that intrinsic septal circuitry is critically involved in the generation of the atropine-sensitive (presumably cholinergic) form of RSA. The mechanisms by which LIA and the two forms of RSA are generated in the hippocampus is discussed.

Distribution of gamma-aminobutyric acid-immunoreactive neurons in the septal region of the rat brain.

The distribution of gamma-aminobutyric acid-immunoreactive (GABA-I) elements was examined in the septal region of the rat brain. The indirect peroxidase-antiperoxidase technique was used with anti-GABA antibodies in normal and colchicine-pretreated rats, with or without use of detergent in the incubation medium. Intraventricular injection of colchicine did not result in any change in the staining of neuronal perikarya. Intraseptal injections increased the intensity of labelling of GABA-I cell bodies in the lateral septal nucleus and increased the number of labelled cells in the medial septal nucleus and diagonal band of Broca (dbB). Triton X-100 added to the incubation media decreased the intensity of staining and number of GABA-I somata in all septal nuclei with a concentration-dependent effect. No change was observed concerning GABA-I varicosities. The septal area, including the lateral, medial, and triangular septal nuclei; the anterior rudiment of the hippocampus; the island of Calleja magna; the septofimbrial nucleus; the bed nucleus of the stria terminalis; and the dbB showed a strong reaction to anti-GABA antibodies with regard to GABA-containing surrounding structures. GABA-I axonal varicosities were observed in all the regions with an uneven distribution. The highest density was found in the dorsal and ventral parts of the lateral septal nucleus and in a band situated between the dbB and the nucleus accumbens. Labelled varicosities were frequently observed surrounding GABA-I and nonimmunoreactive cell bodies. GABA-I somata ranged from 10 to 30 micron in diameter. Small neurons were present in great number at the ventricular border and in the zona limitans. Medium-size and large neurons were mostly observed in the medial part of the dorsal lateral nucleus and in the intermediate lateral nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of acute intraseptal injection of haloperidol in vivo on hippocampal cholinergic function in the mouse

Acute injection of haloperidol into the lateral septum in mice produced an immediate and long-lasting increase in hippocampal sodium-dependent high-affinity choline uptake. Parallel electrophysiological investigations revealed that the increased septo-hippocampal cholinergic activity augmented CA1 pyramidal cell excitability and also accelerated the extinction of a conditioned reinforcement. These results constitute further evidence that septal dopaminergic terminals, via their control of septo-hippocampal cholinergic activity play a significant role in the modulation of hippocampal function.

Intraseptal morphine potentiates pentobarbital narcosis and hypothermia in the rat

Morphine injected intraseptally in the amounts of 35 and 70 nmol prolonged pentobarbital-induced narcosis in the rat. Pentobarbital-induced hypothermia was also potentiated by intraseptal injection of 70 nmol of morphine. These effects were antagonized when morphine was injected together with naltrexone (29 nmol). Naltrexone injected by itself into the septum did not significantly affect pentobarbital-narcosis and hypothermia. It is concluded that activation of mu opioid receptors in the septal region could affect the actions of pentobarbital.

Intraseptal anesthesia in periodontal surgery

This study discusses the rationale, describes the technique, and clinically evaluates the effectiveness of intraseptal injection for surgical procedures, such as open flap curettage. An alternative to conventional local infiltration or regional nerve block injection of anesthesia can be used with efficacy and safety.

The effects of systemic and intraseptal injections of sodium amylobarbitone on rearing and ambulation in rats

Abstract This paper addresses the possibility that anxiolytic drugs, septal lesions and hippocampal lesions have common effects which could (a) he described as an interference with exploration and (b) be attributed to a common interference with the control of hippocampal theta rhythm. Sodium amylobarbitone (20 mg/Kg, i.p.) reduced rearing in a low stress open field test and had complex effects on ambulation. Injection of 0.01 μg amylobarbitone into the medial septum reproduced the effects of systemic injection on ambulation but did not affect rearing. Injection of procaine into the medial septum, which blocks theta rhythm, blocked the habituation of ambulation in a manner similar to that reported for large septal lesions but did not block rearing. It was concluded that the effects of amylobarbitone on ambulation depend on different mechanisms from its effects on rearing and that rearing survives medial septal blockade. Thus amylobarbitone, septal lesions and presumably hippocampal lesions affect explorato...

The effect of intraseptally applied vasopressin on thermoregulation in the rat

The thermoregulatory effects of intraseptal injection of arginine vasopressin were studied in eight rats in which a thermode and a bilateral cannula had been chronically implanted into the preoptic area and lateral septa, respectively. Intraseptal injection of vasopressin completely suppressed the increase in heat production and body temperature elicited by cooling the preoptic area, but did not appear to affect vasomotor tone. Vasopressin also inhibited heat production in a cold environment, and thus induced a marked drop in core temperature; skin temperature did not, however, fall as much as core temperature suggesting that some vasodilatation occurred. At an ambient temperature in the upper range of thermoneutrality vasopressin had no effect on the thermoregulatory variables studied. It is concluded that vasopressin does not reduce the normal set point temperature and that its main effect is to inhibit thermoregulatory heat production. This effect may explain its antipyretic action.

Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning.

The effects of intraseptal scopolamine hydrobromide injections on Pavlovian (classical) conditioning were evaluated, with tones used as the conditioned stimulus (CS) and a periorbital electric shock train as the unconditioned stimulus (UCS). Eye blink (EB) and heart rate (HR) conditioned responses were concomitantly recorded. Although injections of scopolamine into the medial septum impaired the acquisition of the Pavlovian conditioned eyelid reflex, these injections enhanced the magnitude of accompanying Pavlovian conditioned HR decelerations. However, scopolamine applied to the lateral septal area had no effect on EB conditioning, relative to the vehicle, but, like medial injections, enhanced the magnitude of the accompanying HR decelerations. These results are compatible with those of previous investigations: Medial septal dysfunction impairs somatomotor conditioning but leaves autonomic conditioning intact, and septal dysfunction produces a parasympathetic bias of the cardiovascular system.

GABAergic agents on the medial septal nucleus affect hippocampal theta rhythm and acetylcholine utilization

Neurons of the medial septal nucleus are important in regulating the physiological activity of the hippocampus. If intraseptal injection of putative neurotransmitter substances affects the turnover rate of hippocampal acetylcholine, then concomitant changes would be expected in the electrophysiologic activity of the hippocampus. A GABA agonist, muscimol, was injected into the medial septum of rats and the effects on hippocampal electrical activity and acetylcholine utilization were studied. The intraseptally injected muscimol (100 ng) resulted in hippocampal electrographic records containing low amplitude asynchronous waves and significantly less rhythmic slow activity (RSA, 6–9 Hz), compared to control injections of saline. This effect was antagonized by prior intraseptal injection of bicuculline (3 μg). The hippocampal electrical activity returned to normal within 100 min. The utilization of acetylcholine was significantly reduced by intraseptal muscimol at times after administration when electrographic activity was also altered, and spontaneous behavioral movement was increased. These results suggest a physiological connection between hippocampal RSA generation and GABAergic mechanisms in the septum.

Effects of local anesthetics on pulpal blood flow in dogs.

Effects of 2% lidocaine with epinephrine (1:100,000) administered by the various local anesthetic techniques--i.e., infiltration, mandibular block, and intraseptal injection--on pulpal blood flow in dogs were determined using the 15 microns radioisotope-labeled microsphere injection method. The pulpal blood flow decreased significantly with all three techniques; however, the most drastic reduction occurred in the molar teeth with the intraseptal injection. When 2% lidocaine without epinephrine was used in the intraseptal injection, pulpal blood flow increased significantly.

Analeptic effects of centrally injected TRH and analogues of TRH in the pentobarbitone-anaesthetized rat

The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 μg total dose) and the analogues RX 77368 (0.01–1.0 μg), CG 3509 (0.1–1.0 μg), DN-1417 (1.0 μg) and MK-771 (1.0 μg) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 μg) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0–5.0 μg), RX 77368 (0.1–1.0 μg) and CG 3509 (0.1–1.0 μg) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 μg) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 μg) and RX 77368 (0.1 μg) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20–100 μg) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.

Behavioral and neurochemical differentiation of specific projections in the septal-hippocampal cholinergic pathway of the rat.

In the rat, an intraseptal injection of the gamma-aminobutyric acid (GABA) agonist muscimol decreases the turnover rate of acetylcholine in the hippocampus and, during extinction of a food-reinforced lever-press response, increases extinction responding in a dose-dependent manner. Intraseptal beta-endorphin decreases the turnover rate of hippocampal acetylcholine through activation of septal GABAergic interneurons and increases extinction responding. On the other hand, intraseptal substance P, which decreases the turnover rate of hippocampal acetylcholine in a manner unrelated to septal GABAergic mechanisms, fails to increase extinction responding. The turnover rate of acetylcholine in various hippocampal regions after intraseptal injection of muscimol and substance P was also studied. Muscimol decreases the acetylcholine turnover rate only in the ventral hippocampus, whereas substance P decreases it only in the dorsal hippocampus. We hypothesize that a lowering in the cholinergic input to the ventral hippocampus is capable of increasing extinction responding, whereas a decrease in the input to the dorsal hippocampus is without such an effect. Hence, the cholinergic projections to the two hippocampal areas are modulated by different transmitter systems and have different physiological functions.

An immunohistochemical study on the location of GABAergic neurons in rat septum.

Antisera against L-glutamate decarboxylase (GAD), the synthesizing enzyme of gamma-aminobutyric acid (GABA) were used to locate GABAergic neurons and nerve terminals in the septal complex of the rat by using the peroxidase-antiperoxidase method. Varying densities of immunoreactive terminals were observed in saline-treated rats but nerve cell bodies were only demonstrated after interventricular or intraseptal injections of colchicine. Small and medium-sized GAD-positive neurons were found in lateral septal nuclei, the largest number of these cells being in the pars dorsalis, and in the bed nucleus of the stria terminalis. Several GAD-immunoreactive neurons were located in the medial septal nucleus and the nucleus of the diagonal band of Broca (DB), where the cells were larger in the ventral than dorsal parts of the region. In the medial septal nucleus and in DB the GAD-positive cell bodies were distributed similarly to cholinergic neurons. Large GAD-positive neurons were also found in the septofimbrial nucleus. Intense immunoreactivity in nerve terminals was observed in the lateral septal nucleus, around the island of Calleja magna, between the DB and nucleus accumbens, and in the septofimbrial and triangular septal nuclei. In contrast, the medial septal nucleus, the DB, and the bed nucleus of the stria terminalis only showed weak to moderate immunoreactivity. These results provide direct morphological evidence for the presence of neurons capable of synthesizing GABA in septal nuclei. We suggest that there are two different GABAergic neuronal systems operating in the septum: a population of small cells in the lateral septal nucleus and a group of large cells in the medial septum and DB.