sfn2002

Ohara PT, Boudah A, Jasmin L (2002) Long-term effects on pain behavior of decreased spinal noradrenaline in neuropathic rats. Neuroscience 2002 Abstracts 351.22. Society for Neuroscience, Orlando, FL.

Summary: We sought to determine if a permanent reduction in the noradrenergic (NA) input to the spinal cord in adult rats would alter the pain behavior associated with nerve injury. Selective NA denervation of the lumbo-sacral cord was achieved by intrathecal injection of anti-dopamine beta-hydroxylase antibodies conjugated to the toxin saporin in 12 female rats. Spinal NA denervation was confirmed histologically in all animals. Saline injected rats served as controls. Two weeks after toxin or saline treatment, a unilateral peripheral neuropathy was induced by tight ligation of the left L5 spinal nerve in both groups. Unexpectedly, the same degree of mechanical hyperalgesia was present in the neuropathic paw of rats in both the toxin and saline treated groups. Rats lacking NA spinal afferents, however, were less responsive to the antinoiceptive effects of morphine administered systemically or intracerebroventricularly. Also, toxin treated rats did not display opioid dependant stress analgesia. Finally, toxin treated rats were more responsive to the antinociceptive effect of the NK1 antagonist CP 96,345 but not to its enantiomer CP 96,344. From these results we conclude that the permanent loss of spinal NA does not alter neuropathic pain behavior, possibly because of compensatory changes in the CNS. The decreased response to opioids is consistent with the previous suggestions of an interaction between noradrenergic and opioidergic systems in producing analgesia. The increased response to NK1 antagonists shows that NA tonically inhibits substance.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Yoder RM, Pang KCH (2002) Effects of gabaergic or cholinergic medial septal lesions on anxiety. Neuroscience 2002 Abstracts 378.1. Society for Neuroscience, Orlando, FL.

Summary: The hippocampus (HPC) is a structure important for spatial learning and memory. GABAergic and cholinergic neurons in the medial septal area (MSA) provide the two major projections to HPC. Complete destruction of HPC or MSA impairs spatial memory. MSA lesions have an anxiolytic effect, and rats with MSA damage appear be more exploratory. Spatial learning and memory may therefore be influenced by anxiety information reaching HPC through MSA. The present study assessed the effects of MSA GABAergic or cholinergic lesions on anxiety in the elevated plus maze and open-field task. Control rats received intraseptal saline; GABAergic lesions were induced by intraseptal domoic acid; cholinergic lesions were induced by intraseptal 192 IgG-saporin. An elevated plus maze was constructed with 2 open arms and 2 closed arms. Following habituation, each rat was placed in the center of the maze, then observed for 5 minutes. Time spent in the open vs. closed arms and number of entries into open vs. closed arms were compared between groups. The open-field task utilized a square arena with center and outer sections delineated on the floor. Following habituation, each rat was placed into the outer section, then observed for 5 minutes, during which the number of line crossings and amount of time spent in center vs. outer sections were calculated for comparison between groups. In both tasks, frequency of freezing, rearing, head dips, stretched-attend posture, grooming, and defecation was also compared between groups. Results of the present study may help elucidate the role of MSA in the effects of anxiety on learning and memory.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Wright KM, Yoder RM, Pang KCH (2002) Spatial strategies in rats with cholinergic or GABAergic lesions of the medial septum. Neuroscience 2002 Abstracts 378.2. Society for Neuroscience, Orlando, FL.

Summary: The major projection neurons of the septohippocampal (SH) system are GABAergic and cholinergic. When both populations of neurons are damaged together, deficits in learning and memory occur. However, when only one population is damaged, spatial memory in the water maze and radial arm maze is intact. The present study evaluated whether spatial strategies differed between rats with either GABAergic or cholinergic septal lesions. Domoic acid or 192 IgG saporin (sap) was injected into the medial septum (MS) to damage GABAergic or cholinergic neurons, respectively. Spatial strategies were examined on the plus maze and water maze. In the plus maze, rats were started from a single arm and trained to enter a goal arm containing both the reward and an intra-maze cue. Probe trials assessed whether the rats used place, response or cue strategies. During a probe trial, the starting location and the intra-maze cue were moved from that during training. In the water maze, animals were trained for 9 days in 3-day cycles. The first two days of the cycle used a visible platform and the third day of training was performed with a submerged platform. A single probe trial was conducted on day 10. On the probe trial, the first quadrant visited determined whether rats were using cue, place, or response strategies. Preliminary results show that rats treated with domoic acid use the place strategy on all probe trials in the plus maze, but do not use a consistent strategy in the water maze. Sap-treated animals also use mainly a place strategy. The results of this study may help determine the role of MS neurons in spatial strategy selection.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Mohapel P, Leanza G, Lindvall O (2002) Alterations in forebrain acetylcholine influence hippocampal neurogenesis in the adult rodent. Neuroscience 2002 Abstracts 23.9. Society for Neuroscience, Orlando, FL.

Summary: Little is known about how various experiential, environmental and pathological factors regulate neurogenesis in the adult hippocampus. Since the hippocampus receives abundant cholinergic innervation and contains some of the densest distributions of acetylcholine (ACh) fibers, we investigated its potential role in adult neurogenesis. Adult rats received multiple bromodeoxyuridine (BrdU) injections 3 weeks following lesions of the adult rodent forebrain cholinergic projections by intracerebroventricular infusions of 192 IgG-saporin. The day following BrdU administration we observed a significant 20% to 30 % decrease in proliferation in the subgranular cell layer of the dentate gyrus with ACh lesioning. This decrease persisted through to 4 weeks after BrdU administration, when most proliferated cells co-expressed neuronal markers. Conversely, in a separate experiment, naive rats receiving simultaneous injections of the ACh agonist physostigmine and BrdU demonstrated a 30 % increase in proliferated cells (1 day later) and neurons (4 weeks later) in the subgranular cell layer. Our data indicate that cholinergic mechanisms in the forebrain are involved in the regulation of neurogenesis and that this effect may be indirect or direct in the hippocampus.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Zambon NJ, Liberatore MA, Nagle RA, Pokala VN, Li P, Johnson DA (2002) Steroid sulfatse inhibition potentiates working memory deficit induced by 192 IgG-saporin. Neuroscience 2002 Abstracts 82.6. Society for Neuroscience, Orlando, FL.

Summary: Infusion of 192 IgG-saporin (SAP) into the medial septum (MS) of rats selectively lesions cholinergic neurons and impairs acquisition of a delayed matching to position T-maze task. Since steroid sulfatase inhibitors allosterically inhibit the GABA-A receptor and enhance cognition, the present study investigated the cognitive effects of sulfatase inhibition on SAP lesioned animals. Male Sprague-Dawley rats received intraseptal infusions of either cerebrospinal fluid (CSF) or 0.22 μg/μl SAP. Eight days after the infusion, the rats were given an IP injection of either the steroid sulfatase inhibitor DU-14 (30mg/ml) or vehicle daily for 14 days, then every other day during the testing period. In the acquisition phase of testing, each rat completed 8 trial pairs per day until reaching criterion (15 of 16 correct choices). The rats were then tested for retention of the task by inserting delays of 10, 20, and 30 seconds after the first trial of a pair. DU-14 potentiated the impairment in acquisition produced by SAP. The introduction of a delay resulted in deceased performance in all treatment groups except rats administered DU-14 without SAP lesioning. These results suggest that DU-14 may enhance cognition in cholinergically intact animals, but the combination of DU-14, with cholinergic lesioning of MS, impairs working memory by inhibition of both cholinergic and GABAergic neurotransmission.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Pokala VN, Libertore MA, Zambon NJ, Nagle RA, Li PK, Witt-Enderby PA, Johnson DA (2002) Effect of 192 IgG-saporin medial-septum lesion on hippocampal receptor density in rats. Neuroscience 2002 Abstracts 82.7. Society for Neuroscience, Orlando, FL.

Summary: The aim of the study was to quantify the effect of selective cholinergic neurotoxin192 IgG-saporin (SAP) medial septal (MS), lesions on hippocampal muscarinic, GABAA and NMDA receptor density. Rats were injected with SAP (0.22 and 0.45 μg/μl) into the MS. After 6 weeks, hippocampal tissue was collected and saturation radioligand binding assays were performed to determine the receptor density. 3H-QNB was a muscarinic antagonist, 3H-muscimol a GABAergic agonist and 3H-MK-801 an NMDA antagonist were utilized. The results demonstrated a dose dependent increase in muscarinic receptor density (B-max) of 226 and 355% respectively. These results suggest changes in receptor density in response to hippocampal cholinergic denervation.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Chang Q, Gold PE (2002) Residual hippocampal cholinergic functions after 192 IgG-saporin lesions of the medial septum/ventral diagonal band (MS/VDB). Neuroscience 2002 Abstracts 82.8. Society for Neuroscience, Orlando, FL.

Summary: 192 IgG-saporin (SAP) injections into the MS/VDB reportedly destroy acetylcholine (ACh) neurons projecting to hippocampus (HC) without associated impairments of learning and memory on HC-dependent tasks. These findings contrast sharply with those obtained with many other methods showing close associations between ACh functions in the HC and learning and memory. The present experiment addressed this conflict. SAP was injected into MS/VDB 1 week before the start of neural and behavioral measures. We found: 1) Using in vivo microdialysis, release of ACh in the HC was not abolished but was ~30% of control values. The percent increase in ACh release during spontaneous alternation testing was greater in SAP-treated than in control rats. 2) SAP-treated rats had significant impairments on the HC-dependent alternation task. Moreover, intra-HC injections of physostigmine (20 ng in 1 µl), an indirect ACh agonist, enhanced alternation scores. 3) Physostigmine (0.6 mg/kg, IP) induced more intense tremors in SAP-treated than in control rats. 4) While SAP-treated rats had near-total depletion of cells in MS/VDB stained using immunocytochemistry for choline acetyltransferase (ChAT), quantitative densitometry showed no depletion of ChAT staining in either CA1 or the dentate gyrus in the SAP group. These findings suggest that there are residual and even heightened ACh functions which can compensate for the insult of MS/VDB SAP lesions, complicating the use of this lesion to evaluate the role of septohippocampal cholinergic projections in learning, memory or other functions.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Wu M, Xu C, Alreja M (2002) Physiological and pharmacological characteristics of the inhibitory muscarinic response in septohippocampal cholinergic neurons. Neuroscience 2002 Abstracts 35.7. Society for Neuroscience, Orlando, FL.

Summary: Septohippocampal cholinergic neurons in the MSDB provide the hippocampus with almost its entire ACh and also release ACh locally within the MSDB. The released ACh sustains activity in the GABAergic limb of the septohippocampal pathway. Septohippocampal cholinergic neurons undergo atrophy in neurodegenerative disorders associated with loss of cognition. In a recent study we demonstrated that 65% of septohippocampal cholinergic neurons are inhibited by ACh via muscarinic receptors. Because of the importance of ACh and septohippocampal cholinergic neurons in cognition, we studied the physiological and pharmacological properties of the muscarinic response in MSDB neurons. Using intracellular and whole-cell recordings, we tested the effects of muscarine on retrogradely-labeled septohippocampal cholinergic neurons in vitro in rat brain slices. The cells were labeled using the Cy3-192IgG, a selective marker of septohippocampal cholinergic neurons. Prolonged (10-15 mins) but not short (1-2 min) applications of muscarine or oxotremorine produced a marked desensitization (>50%). The muscarine-induced outward current was found to be mediated via direct as well as indirect mechanisms. It reversed at Ek and was blocked by external barium. The M2/M4 antagonist, methoctramine blocked the muscarine response in only 10% of the neurons tested and tropicamide, an M4-prefering antagonist, blocked the muscarine response in 5/5 neurons tested, suggesting possible involvement of M4 receptors.

Related Products: 192-IgG Mouse Monoclonal, Cy3-labeled (Cat. #AB-N43FL3)

Seki S, Erickson KA, Sasaki K, Sugaya K, Chancellor MB, de Groat WC, Yoshimura N (2002) Effect of intrathecal substance P-saporin conjugate on bladder hyperactivity induced by intravesical capsaicin. Neuroscience 2002 Abstracts 68.2. Society for Neuroscience, Orlando, FL.

Summary: Substance P and neurokinin 1 (NK1) receptors in the spinal cord reportedly play an important role in the micturition reflex as well as in nociceptive responses. We investigated the effect of elimination of NK 1 receptor-expressing spinal cord neurons using the substance P-saporin conjugate (SSP-SAP) on the micturition reflex. Using female rats, an intrathecal catheter was implanted at the level of the L6-S1 spinal cord for injection of either 8 µl of saporin (1.5 µM) or SSP-SAP (1.0 µM). Awake cystometry performed 3 weeks after injection showed no changes in normal bladder function in saporin and SSP-SAP-treated rats. When bladder hyperactivity was induced by intravesical instillation of capsaicin (15 µM), the reduction of intercontraction interval (ICI) was significantly smaller (43.0 ± 6.2% of reduction) in SSP-SAP-treated rats than in saporin-treated rats (59.3 ± 3.1%). Immunohistochemical staining revealed that the area positively stained with NK1 receptor antibodies in the lamina I of the dorsal horn was significantly reduced by 34% in SSP-SAP treated rats, compared with saporin-treated rats. These results suggest that NK1 receptor-expressing neurons in the dorsal horn of the spinal cord play an important role in inducing bladder hyperactivity elicited by intravesical capsaicin. Thus elimination of NK1 receptor-expressing neurons in the spinal cord using SSP-SAP at this concentration could be effective to treat bladder hyperactivity induced by bladder irritation without affecting normal bladder function.

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Ricceri L, Moles A, Pezzola A, Popoli P, Calamandrei G (2002) Neonatal basal forebrain cholinergic lesions disrupt retention of socially transmitted food preferences and alter EEG activity in adult rats. Neuroscience 2002 Abstracts 82.9. Society for Neuroscience, Orlando, FL.

Summary: Previous studies using selective neonatal lesions of basal forebrain cholinergic neurons showed mild long-term effects on spatial discrimination capabilities, whereas water maze learning appeared intact. In the present study we examined long-term effects of icv injections of 192 IgG saporin performed in 7-day-old rats on the social transmission of food preferences (a form of non-spatial associative memory) at adulthood. In 6-month-old rats the neonatal cholinergic lesion impaired 4-h and 24-h retention of a learned social food preference relative to controls, despite performance on an immediate retention trial was indistinguishable from controls. A second experiment excluded alterations in neophobia towards unfamiliar scented food after neonatal cholinergic lesions: level of novel food consumption did not differ between neonatally saporin-lesioned and control rats. Computerized EEG spectral analysis (FFT transform) performed in 6-month-old rats revealed that the neonatal cholinergic lesions increased δ power and reduced β power in both fronto-parietal and parieto-occipital cortex. Effectiveness of the neonatal lesion was confirmed by a marked cholinergic loss in both hippocampal and cortical regions. Altogether, behavioral and electrophysiological data suggest that the neonatal cholinergic lesion of the basal forebrain – more than the adult one – could represent a useful experimental model of Alzheimer-like memory dysfunctions.

Related Products: 192-IgG-SAP (Cat. #IT-01)