Intraseptal Injection Research Articles

Investigating the Co-administration of Ghrelin and Nicotine into the Medial Septum and Its Influencing on Morphine Amnestic Effect

Introduction: Evidence indicates that medial septum nicotinic receptors regulate cognitive processes. Ghrelin is a gut hormone that regulates energy homeostasis. Ghrelin is also produced in the brain and is involved in cognitive function. This study aims to evaluate the effects of medial septal administration of ghrelin on the amnestic effect of morphine in rats.In addition, the possible relationship between the medial septal ghrelin and acetylcholine nicotinic receptors on the amnestic effect of morphine is evaluated. Methods: The rats were implanted at the medial septum area and were microinjected with ghrelin and nicotinic receptor agents. The step-through type inhibitory avoidance apparatus was used for memory retrieval assessment. Results: The results showed that the administration of morphine after the training phase impaired memory consolidation. Post-training intra-septal injection of the same doses of either ghrelin or nicotine did not change memory performance; however, their co-application with morphine (significant dose: 7.5 mg/kg subcutaneous injection) increased the step-through latency and improved memory consolidation. Moreover, post-training co-application of low doses of the two agonists could not affect morphine-induced memory impairment. Conclusion: These results indicated no interaction between medial septal ghrelin and nicotinic receptors on the amnestic effect of morphine in rats.

Anesthetic efficacies of buccal with palatal injection versus buccal with intra-septal injection in permanent maxillary first molars of pediatric patients.

The high success rate of dental treatment is dependent on the cooperation of pediatric patients during procedures. Dental treatment often causes pain, particularly in children. The factors in providing treatment to pediatric patients include the characteristics and location of the tooth, profoundness of the anesthesia including the type of local anesthetic, and cooperation of the patient. Previous studies have examined several techniques to successfully achieve profound pulpal anesthesia in maxillary permanent teeth. The dentist should select the injection technique to be used based on patient needs. In children, either buccal with palatal injections or buccal with intra-septal injections may be used to anesthetize the permanent maxillary first molar. Buccal with palatal injections are commonly used prior to routine maxillary dental procedures. Currently, there are only a few studies on the employment of buccal with intra-septal injections to anesthetize permanent maxillary first molars in pediatric patients. This review will focus on efficacy of buccal with palatal versus buccal with intra-septal pulpal anesthesia of the permanent maxillary first molars in pediatric patients and aim to determine which technique should be used during routine dental procedures.

Intrahippocampal Adeno-Associated Virus-Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin-Induced Impairments of Hippocampal Plasticity and Behavior.

One of the aspects of Alzheimer disease is loss of cholinergic neurons in the basal forebrain, which leads to development of cognitive impairment. Here, we used a model of cholinergic deficit caused by immunotoxin 192IgG-saporin to study possible beneficial effects of adeno-associated virus (AAV)–mediated overexpression of nerve growth factor (NGF) in the hippocampus of rats with cholinergic deficit. Suspension of recombinant AAV carrying control cassette or cassette with NGF was injected into both hippocampi of control rats or rats with cholinergic deficit induced by intraseptal injection of 192IgG-saporin. Analysis of choline acetyltransferase (ChAT) immunostaining showed that NGF overexpression in the hippocampus did not prevent strong loss of ChAT-positive neurons in the septal area caused by the immunotoxin. Induction of cholinergic deficit in the hippocampus led to impairments in Y-maze and beam-walking test but did not affect behavioral indices in the T-maze, open field test, and inhibitory avoidance training. NGF overexpression in the rats with cholinergic deficit restored normal animal behavior in Y-maze and beam-walking test. Recording of field excitatory postsynaptic potentials in vivo in the hippocampal CA1 area showed that induction of cholinergic deficit decreased magnitude of long-term potentiation (LTP) and prevented a decrease in paired-pulse ratio after LTP induction, and NGF overexpression reversed these negative changes in hippocampal synaptic characteristics. The beneficial effect of NGF was not associated with compensatory changes in the number of cells that express NGF receptors TrkA and NGFR in the hippocampus and medial septal area. NGF overexpression also did not prevent a 192IgG-saporin–induced decrease in the activity of acetylcholine esterase in the hippocampus. We conclude that NGF overexpression in the hippocampus under conditions of cholinergic deficit induces beneficial effects which are not related to maintenance of cholinergic function.

Long-term potentiation in the hippocampal CA3 to CA1 synapses may be induced in vivo by activation of septal cholinergic inputs

Purpose/aim The role of cholinergic neurotransmission in the hippocampus remains controversial since different studies showed either no influence or its modulatory effect on glutamatergic hippocampal synapses. It remains unclear whether septal cholinergic input can modulate plasticity of synapses formed by CA3 pyramids on CA1 neurons. The aim of the study was to clarify the role of septal input in the development of LTP in this synapse. Materials and methods We recorded in vivo in rats under urethane anesthesia focal excitatory postsynaptic potential (fEPSP) characteristics in CA1 area after stimulation of the ventral hippocampal commissure (VHC), which contains both CA3 axons innervating CA1 neurons and cholinergic axons coming from the medial septum. We performed two series of experiments in which LTP was induced by tetanization of either VHC or medial septal area (MSA). Degeneration of cholinergic neurons in MSA was induced by intraseptal injection of 192IgG-saporin. Results In both experimental series, tetanization induced an increase in fEPSP amplitude which lasted for at least 40 min after tetanic stimulation, although tetanization of VHC induced a larger increase in fEPSP amplitude compared to MSA tetanization. Elimination of septal cholinergic neurons by 192IgG-saporin abolished LTP development in both experimental series. This suppression of LTP in animals with cholinergic deficit was not due to loss of hippocampal neurons. Conclusions Our data suggest that activation of septal cholinergic fibers during tetanization is a critical factor of LTP induction in the hippocampal CA3 to CA1 synapses.

Enhancement of muscle relaxant effect of rocuronium by intraseptal injection of a solution containing lidocaïne and epinephrine : a case report

Introduction : Various drugs and physiologic disturbances affect the action of neuromuscular blocking agents. If some are ignored by the anesthesiologist, e.g. in the absence of monitoring of neuromuscular function, the patient may be at risk of potentially severe consequences related to postoperative residual curarization. Case presentation : A 67-year-old female patient underwent septoplasty under general anesthesia with basic monitoring (three-lead electrocardiogram, non-invasive blood pressure, end-tidal partial pressure of carbon dioxide and SpO2) and a monitoring of neuromuscular function using acceleromyography of the adductor pollicis. General anesthesia was induced with propofol and sufentanil. After neuromuscular monitoring calibration, a single dose of rocuronium was given. Thereafter the trachea was intubated and anesthesia was maintained with sevoflurane. One hundred and two minutes after the administration of rocuronium, a 1% lidocaine solution containing 5µg/mL epinephrine was injected under the mucosa of the nasal septum immediately before the incision. Two minutes after this injection, the train of four ratio was significantly reduced. It took about 13 minutes to recover to the value recorded before the submucosal injection. Conclusion : Epinephrine increases the degree of muscle relaxation achieved by rocuronium, even when neuro-muscular function is recovering. Monitoring is the only mean to rule out a risk of postoperative residual curarization, given the numerous medications and factors interfering with the action of neuromuscular blocking agents.

Impact of maxillary teeth morphology on the failure rate of local anesthesia.

Objective:To investigate the effect of maxillary single and multiple rooted teeth on the success rate of buccal infiltration anesthesia.Subjects and Methods:This clinical study was performed by dividing the participants into three groups. Group one included 30 patients with upper anterior teeth, group two 23 patients with upper premolars teeth and group three 39 patients with upper molars for extraction. Onset time of anesthtic action was evaluted by using electronic pulp tester. Pulp testing assessments were carried out immediately before the injection and at the intervals of 2 mins following the injection until the anesthetic success obtains.Results:Seventy-nine patients in this study secured anesthetic success within study duration time (10 min). However, there were 13 patients with dental anesthesia failures (3 patients with single rooted teeth and 10 patients with multiple rooted teeth). There were no significant differences in the mean onset time of pulpal anesthesia between the anterior, middle and posterior teeth (P value = 0.449). Clinically, patients with single rooted teeth reported faster dental anesthesia and earlier teeth extraction than patients with multiple rooted teeth.Conclusion:This study showed that the single rooted teeth have faster pulpal anesthesia and early extraction than teeth with multiple roots but not statistically significant. Administration of extra local anesthetic cartridge or using intraseptal injection technique can be a solution to overcome the failure of anesthesia in the maxillary posterior teeth.

How Successful is Supplemental Intraseptal and Buccal Infiltration Anaesthesia in the Mandibular Molars of Patients Undergoing Root Canal Treatment or Tooth Extraction?

ABSTRACTObjectivesTo investigate the success rate of supplemental intraseptal and buccal infiltration anaesthesia in mandibular molars undergoing endodontic therapy/extraction when the inferior alveolar nerve block has failed.Material and MethodsA prospective clinical trial including 200 patients undergoing lower molar root canal treatment/teeth extraction was conducted. Only 80 patients of the participants who had profound lower lip anaesthesia after the administration of inferior alveolar nerve block (IANB) were in pain within treatment. Patients experiencing moderate to severe pain upon using elevators, forceps, bur, or endodontic file were randomly allocated to the 2% lidocaine intraseptal injection and 4% articaine buccal infiltration groups. Level of pain was assessed every 2 to 10 min on standard 100 mm visual analogue scales.ResultsOverall, 55 (69%) of patients who were given either intraseptal injection of 2% lidocaine or buccal infiltration of 4% articaine had successful anaesthesia of lower molar teeth within 10 min. However, 25 (31%) of participating patients in the buccal infiltration and the intraseptal groups had failed anaesthesia within the study duration (10 min), and they received additional local anaesthetic. IANBs were more painful than buccal and intraseptal injections. However, buccal articaine injections were significantly more comfortable than intraseptal lidocaine injections (P > 0.001).ConclusionsSupplemental intraseptal injection of 2% lidocaine and buccal infiltration of 4% articaine achieved profound pulpal anaesthesia in 69% of patients when the inferior alveolar nerve block failed. Recommendations can be given to dental practitioners to use infiltration of 4% articaine in conjunction with intraseptal injection of 2% lidocaine to anaesthetize the lower molar teeth when inferior alveolar nerve block fails.

Effects of Cholinergic Lesions and Cholinesterase Inhibitors on Aromatase and Estrogen Receptor Expression in Different Regions of the Rat Brain

Cholinergic projections have been shown to interact with estrogens in ways that influence synaptic plasticity and cognitive performance. The mechanisms are not well understood. The goal of this study was to investigate whether cholinergic projections influence brain estrogen production by affecting aromatase (ARO), or influence estrogen signaling by affecting estrogen receptor expression. In the first experiment, ovariectomized rats received intraseptal injection of the selective immunotoxin 192IgG-saporin to destroy cholinergic inputs to the hippocampus. In the second experiment ovariectomized rats received daily intraperitoneal injections of the cholinesterase inhibitors donepezil or galantamine for 1 week. ARO activity and relative levels of ARO, ERα, ERß, and GPR30 mRNAs were quantified in the hippocampus, frontal cortex, amygdala and preoptic area. Results show that the cholinergic lesions effectively removed cholinergic inputs to the hippocampus, but had no significant effect on ARO or on relative levels of ER mRNAs. Likewise, injections of the cholinesterase inhibitors had no effect on ARO or ER expression in most regions of the brain. This suggests that effects of cholinergic inputs on synaptic plasticity and neuronal function are not mediated by effects on local estrogen production or ER expression. One exception was the amygdala where treating with galantamine was associated with a significant increase in ARO activity. The amygdala is a key structure involved in registering fear and anxiety. Hence this finding may be clinically relevant to elderly patients who are treated for memory impairment and who also struggle with fear and anxiety disorders.

How Effective Is Supplemental Intraseptal Anesthesia in Patients with Symptomatic Irreversible Pulpitis?

IntroductionPrevious studies have reported high levels of success with intraseptal injection for various dental procedures but provide limited information on the use of the injection during endodontic treatment. Therefore, the purpose of this prospective study was to determine the anesthetic efficacy of the supplemental intraseptal technique in mandibular posterior teeth diagnosed with symptomatic irreversible pulpitis when the conventional inferior alveolar nerve (IAN) block failed. MethodsOne hundred patients with a diagnosis of symptomatic irreversible pulpitis in a mandibular posterior tooth were recruited. Following profound lip numbness after the administration of the conventional IAN block, endodontic treatment was initiated. Patients still experiencing moderate to severe pain during treatment were administered mesial and distal supplemental intraseptal injections using 0.7 mL 4% articaine with 1:000,000 epinephrine administered with a computer-controlled local anesthetic delivery unit. Success was defined as the ability to perform endodontic access and instrumentation with mild to no pain. ResultsSuccess with the IAN block was achieved in 25% of patients. Supplemental intraseptal injections provided success in 29% of patients. ConclusionsSupplemental intraseptal injections achieved profound pulpal anesthesia in 29% of patients when the IAN block failed. This low level of success would not provide predictable levels of anesthesia for patients requiring emergency endodontic treatment for symptomatic irreversible pulpitis in mandibular posterior teeth.

The recombinant C-terminal fragment of tetanus toxin protects against cholinotoxicity by intraseptal injection of β-amyloid peptide (25–35) in rats

The recombinant C-terminal domain of tetanus toxin (Hc-TeTx) is a new non-toxic peptide of the tetanus toxin that exerts a protective action against glutamate excitotoxicity in motoneurons. Moreover, its efficacy as a neuroprotective agent has been demonstrated in several animal models of neurodegeneration. The eleven amino acids in the β amyloid peptide (Aβ25–35) mimic the toxic effects of the full β amyloid peptide (Aβ1–42), causing the impairment of the cholinergic system in the medial septum (MS) which, in turn, alters the septo-hippocampal pathway and leads to learning and memory impairments. The aim of this study was to examine the neuroprotective effects of the Hc-TeTx fragment against cholinotoxicity. The Hc-TeTx fragment (100ng) was injected into the rats intercranially, with the Aβ(25–35) (2μg) then injected into their MS. The animals were tested for spatial learning and memory in the eight-arm radial maze. The brains were removed to assess cholinergic markers, such as choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and to explore neurodegeneration in the MS and hippocampus, using amino-cupric silver and H&E staining. Finally, capase-3, a marker of apoptosis, was examined in the MS. Our results clearly demonstrate that the application of Hc-TeTx prevents the loss of cholinergic markers (ChAT and AChE), the activation of capase-3, and neurodegeneration in the MS and the CA1 and CA3 subfields of the hippocampus. All these improvements were reflected in spatial learning and memory performance, and were significantly higher compared with animals treated with Aβ(25–35). Interestingly, the single administration of Hc-TeTx into the MS modified the ChAT and AChE expression that affect cognitive processes, without inducing neurodegeneration or an increase in capase-3 expression in the MS and hippocampus. In summary, our findings suggest that the recombinant Hc-TeTx fragment offers effective protection for the septo-hippocampal pathway, given that it reduces the neurodegeneration caused by Aβ(25–35) and improves learning and memory processes.

Modulation of Pain by Naloxone and a Possible Role of Neurotransmitters with Selective Lesion of Septal Nuclei

Septum occupies a strategic position in limbic system and has been implicated in variety of behaviors. Present study was designed to evaluate the role of medial septum in modulation of pain and explore the role of neurotransmitters. The present study was divided in two parts in first part the tail flick latencies were observed in rats with septal lesions and compared with sham operated ones. While in the second part, the effect of intraseptal injections of neurotransmitters and naloxone on tail flick latencies of cannulated rats was recorded after intraseptal lesions. It was observed that the septal lesions decrease pain threshold. The interaseptal injection of Acetylcholine (5 μg to 20 μg) and Naloxone (5 μg to 20 μg) increases pain threshold. While the Interaseptal injection of Noradrenaline and Scopolamine decreases pain threshold. The findings of the present study suggest that septum may be involved in modulation of pain. The neurotransmitters like Acetylcholine, Noradrenaline and opioid peptides may have an individual or collective role to play in the observed pain modulation.

Сравнение эффективноСти обезболивания пульпита временных моляров нижней челюСти артикаиновым анеСтетиком

Aim.Analyzed the effectiveness of different anaesthetic techniques in the mandible primary teeth. Material and methods. In 180 children aged 3—9 years was189 injections for 207 teeth: inferior alveolar nerve block for 81 teeth (63 injections), mandibular infiltration for 44 primary molars children up to 7 years, and intraseptal injection for 82 primary molars. Used 4% articaine with 1:200 000 epinephrine. Dental procedure included pulpectomies in primary molars. Results.Inferior alveolar nerve blockwas effective in 77,77%, mandibular infiltration in children under 7 years in 61,36%, intraseptal injection was effective in 70,73%. In other cases we had to resort to additional injection, which resulted in a generally positiveresult was obtained in 96,29% of cases. No statistically significant difference was found between the three anaesthetic techniques.

Pyroglutamyl Peptidase II Inhibition Enhances the Analeptic Effect of Thyrotropin-Releasing Hormone in the Rat Medial Septum

Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH(2)) has multiple, but transient, homeostatic functions in the brain. It is hydrolyzed in vitro by pyroglutamyl peptidase II (PPII), a narrow specificity ectoenzyme with a preferential localization in the brain, but evidence that PPII controls TRH communication in the brain in vivo is scarce. We therefore studied in male Wistar rats the distribution of PPII mRNA in the septum and the consequence of PPII inhibition on the analeptic effect of TRH injected into the medial septum. Twelve to 14% of cell profiles expressed PPII mRNA in the medial septum-diagonal band of Broca; in this region the specific activity of PPII was relatively high. Twenty to 35% of PPII mRNA-labeled profiles were positive for TRH-receptor 1 (TRH-R1) mRNA. The intramedial septum injection of TRH reduced, in a dose-dependent manner, the duration of ethanol-induced loss of righting reflex (LORR). Injection of the PPII inhibitor pGlu-Asn-Pro-7-amido-4-methylcoumarin into the medial septum enhanced the effect of TRH. The injection of a phosphinic TRH analog, a higher-affinity inhibitor of PPII, diminished the duration of LORR by itself. In contrast, the intraseptal injection of pGlu-Asp-Pro-NH(2), a peptide that did not inhibit PPII activity, or an inhibitor of prolyl oligopeptidase did not change the duration of LORR. We conclude that in the medial septum PPII activity may limit TRH action, presumably by reducing the concentration of TRH in the extracellular fluid around cells coexpressing PPII and TRH-R1.

Recognition of novel objects and their location in rats with selective cholinergic lesion of the medial septum

The importance of cholinergic neurons projecting from the medial septum (MS) of the basal forebrain to the hippocampus in memory function has been controversial. The aim of this study was to determine whether loss of cholinergic neurons in the MS disrupts object and/or object location recognition in male Sprague-Dawley rats. Animals received intraseptal injections of either vehicle, or the selective cholinergic immunotoxin 192 IgG-saporin (SAP). 14 days later, rats were tested for novel object recognition (NOR). Twenty-four hours later, these same rats were tested for object location recognition (OLR) (recognition of a familiar object moved to a novel location). Intraseptal injections of SAP produced an 86% decrease in choline acetyltransferase (ChAT) activity in the hippocampus, and a 31% decrease in ChAT activity in the frontal cortex. SAP lesion had no significant effect on NOR, but produced a significant impairment in OLR in these same rats. The results support a role for septo-hippocampal cholinergic projections in memory for the location of objects, but not for novel object recognition.

Antidepressant-like effects of mineralocorticoid but not glucocorticoid antagonists in the lateral septum: Interactions with the serotonergic system

The lateral septum (LS) is a limbic brain region that receives serotonergic projections from raphe neurons and participates in the modulation of stress responses and affective states. The present study determined whether mineralocorticoid receptors (MRs) and/or glucocorticoid receptors (GRs) located in the LS interact with the serotonergic system in the regulation of depressive-like behavior of rats subjected to the forced swimming test (FST). We also studied the effect of corticosterone release induced by the FST on MR- and GR-mRNA expression in the LS. Specifically, we studied the antidepressant-like effects of spironolactone (a MR antagonist), mifepristone (a GR antagonist), and the antidepressant clomipramine (CMI) administered directly into the LS. In addition, spironolactone and CMI actions were studied in animals with serotonergic depletion induced by dl-p-chlorophenylalanine (pCPA). Finally, adrenalectomized and Sham-operated rats were subjected to the FST to determine MR- and GR-mRNA expression in the LS at different post-FST intervals. The results showed that intraseptal injection of spironolactone, but not mifepristone induced antidepressant-like actions in the FST; this effect was blocked by pCPA treatment. CMI and spironolactone increased 5-HT concentrations in the LS of rats subjected to the FST. Increases in corticosterone release, induced by the FST, correlated with a decrease in MR-mRNA expression in the LS; no correlation was found with GR-mRNA expression. In conclusion, MRs in the lateral septum, but not GRs, participate in the regulation of depressive-like behavior of animals subjected to the FST. Both serotonin and corticosterone play an important role in MR actions in the LS.

An Audit of the Use of Intra-Septal Local Anaesthesia in a Dental Practice in the South of England

The aim of this audit was to evaluate the efficacy, when used by the author, of the intra-septal local anaesthetic technique for cavity preparation in mandibular molar and premolar teeth. One hundred and thirteen consecutive patients who required local anaesthesia (LA) for cavity preparation in lower molar and premolar teeth in a general dental practice took part in the audit sample. Articaine 4%, with 1:100,000 adrenaline (epinephrine), was administered using the intra-septal technique. Visual analogue scales (VAS) were used to record pain experienced on injection and the quality of anaesthesia obtained. Any side-effects reported were recorded. The standards set were that at least 70% should find the administration of the LA pain-free and that at least 80% should experience no pain during cavity preparation. Sixty-nine (62%) patients reported the injection technique to be completely pain-free and a further 23 (20%) reported very minor pain on injection. Eighty (71%) patients reported pain-free treatment and 18 (16%) experienced very minor pain during treatment. No side-effects were reported. Patients aged under 40 years and those who had cavities prepared in first premolar teeth appeared more likely to experience pain during cavity preparation. The intra-septal injection technique requires no specialist equipment, is easily administered, rapid in onset and provides a level of anaesthesia equivalent to that produced by an inferior dental nerve block and with fewer side-effects. The injection is relatively painless to administer.

Neurokinin2‐R in medial septum regulate hippocampal and amygdalar ACh release induced by intraseptal application of neurokinins A and B

The neurokinin receptors (NK-R), NK(2)- and NK(3)-R, have been implicated in behavioral processes, but apparently in opposite ways: while NK(2)-R agonism disrupts memory and has anxiogenic-like action, NK(3) -R agonists facilitate memory and display anxiolytic-like effects. Systemic application of NK(2)-R antagonists block the release of acetylcholine (ACh) in the hippocampus, which is induced by intraseptal administration of the NK(2)-R ligand, neurokinin A (NKA). We investigated the effects of medial septal injection of NKA and a preferred ligand of NK(3)-R, neurokinin B (NKB), on the activity of cholinergic neurons of the basal forebrain and assessed the role of the medial septal NK(2)-R in the control of extracellular ACh levels in cholinergic projection areas. ACh was dialysed in the frontal cortex, amygdala and hippocampus of anesthetized animals and was analysed by HPLC-EC. ACh levels in hippocampus and amygdala, but not in frontal cortex were increased after intraseptal injection of either NKA or NKB (0.1, 1, 10 μM). Application of the nonpeptidic NK(2)-R antagonist, saredutant SR48968 (1, 10, 100 pM), followed by NKA (1 μM) or NKB (10 μM) injection into the medial septum, blocked the ACh increase in hippocampus and amygdala. These results indicate that medial septal NK(2)-R have an important role in mediating ACh release, for one, via the septal-hippocampal cholinergic projection and, secondly, via direct or indirect route to the amygdala, but not frontal cortex. They also support the hypothesis that hippocampal cholinergic neurotransmission controls amygdala function suggesting that this interaction is regulated via NK(2)-R in the medial septum.

Selective lesions of medial septal GABAergic neurons disrupt Hippocampal Theta Rhythm Amplitude

Septal inputs critically modulate hippocampal function. However, the role of Medial Septal/Diagonal Band (MS/DB) neuronal populations in hippocampal theta rhythm generation is still under debate. MS/DB GABAergic neurons selectively innervate inhibitory hippocampal interneurons and through this action exert a powerful control on hippocampal excitability. To further investigate the role of the MS/DB GABAergic neurons in hippocampal theta rhythm generation, the antibody Gamma amino butyric acid Transporter 1 (GAT-1) conjugated to saporin (SAP, 3µL at 325ng/µL) was injected in the MS/DB of adults Sprague Dawley rats to selectively destroy GABAergic neurons. Population estimates of MS/DB GABAergic neurons were analyzed using StereoInvestigator 9. A significant reduction (75%, p<0.0001) in the MS/DB GABAergic population was observed, while the cholinergic and glutamatergic neuronal population were spared. The effects of this GABAergic neuronal loss in hippocampal function were investigated by hippocampal EEG recordings. EEG recordings of freely moving rats were acquired using the Harmonie Stellate monitoring system. EEGs were recorded before and after the intraseptal injection of anti-GAT-1-SAP. Two second duration trace, representative of theta I and theta II were transferred off line to ClampFit 9 software to measure amplitude and produce a power spectrum. After analysis of the theta traces the rat brains were sliced and stereology was once again performed to determine the relationship between the destruction of MS/DB GABAergic neurons and the hippocampal theta rhythm.

Scopolamine- and diazepam-induced amnesia are blocked by systemic and intraseptal administration of substance P and choline chloride

Systemic (IP) and/or intraseptal (IS) administration of scopolamine (SCP) and diazepam (DZP) induce amnesia, whereas IP injection of the neuropeptide substance P (SP) and choline chloride (ChCl) produce memory facilitation. The septohippocampal cholinergic system has been pointed out as a possible site of SCP and DZP-induced amnesia as well as for the mnemonic effects induced by SP and ChCl. We performed a series of experiments in order to investigate the interactions between cholinergic and GABA/benzodiazepine (GABA/BZD) systems with the SPergic system on inhibitory avoidance retention. Male Wistar rats were trained and tested in a step-down inhibitory avoidance task (1.0 mA footshock). Animals received, pre-training, IP (1.0 mg/kg) or IS (1.0 nM/0.5 μl) injection of DZP, SCP (SCP; 1.0 mg/kg – IP or 0.5 μM/0.5 μl – IS) or vehicle (VEH). Immediately after training they received an IP or IS injections of SP 1-11 (50 μg/kg – IP or 1.0 nM/0.5 μl – IS), SP 1-7 (167 μg/kg – IP or 1.0 nM/0.5 μl – IS), ChCl (20 mg/kg – IP or 0.3 μM/0.5 μl – IS) or VEH. Rats pretreated with SCP and DZP showed amnesia. Post-trial treatments with SP 1-11, SP 1-7 or ChCl blocked the amnesic effects of SCP and DZP. These findings suggest an interaction between SPergic and cholinergic mechanisms with GABAergic systems in the modulation of inhibitory avoidance retention and that the effects of these treatments are mediated, at least in part, by interactions in the septohippocampal pathway.

Effects of reversible inactivation of the medial septum on rat exploratory behavior in the elevated plus-maze using a test–retest paradigm

The effect of intraseptal injections of lidocaine before a first or a second session in the elevated plus-maze, in a test–retest paradigm, was investigated. In addition to gross session analyses, a minute-by-minute analysis of the sessions was used to evaluate both anxiety and memory. Lidocaine injections before the test session produced increases in the frequency of entries, time spent and distance run in the open arms without affecting activity occurring in the closed arms. During the retest session, saline- and lidocaine-treated rats exhibited increased indices of anxiety and lidocaine-treated rats exhibited decreased closed-arm entries. The minute-by-minute analysis showed a faster decrease in anxiety-related behaviors during the test session by saline- than by lidocaine-treated rats and a significant decrease in closed-arm exploration by saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection before the retest session produced increases in the frequency of entries, time spent and distance run in the open arms in the second session when compared with saline-treated rats. Minute-by-minute analysis showed an increase in the time spent in the open arms by lidocaine animals at the beginning of the retest session in comparison to saline animals and a significant decrease in closed-arm exploration by both groups. These results suggest that inactivation of the medial septum by lidocaine affects the expression of unconditioned and conditioned forms of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and retention of spatial information.