targeted-toxins

Stowell JR, Bemtson GG, Sarter M (1999) Lesions of basal forebrain cholinergic neurons eliminate the modulatory effects of benzodiazepine receptor ligands on behavioral and cardiovascular reactions in an anxiogenic paradigm. Neuroscience 1999 Abstracts 358.5. Society for Neuroscience, Miami, FL.

Summary: We have previously shown that basal forebrain cortical cholinergic projections mediate potentiation of the cardiovascular defensive response by the putative anxiogenic benzodiazepine receptor partial inverse agonist FG 7142 (Bertnson et al., 1998). The present study assessed the effects of lesions of the basal forebrain cholinergic neurons on operant responding in a conditioned suppression paradigm and the modulating effects of benzodiazepine receptor (BZR) ligands in this paradigm. Nine animals received basal forebrain infusions (0.18 µg/hemisphere) of the immunotoxin 192 IgG-saporin. Lesioned and control (n=9) animals were trained in a conditioned suppression paradigm using a tone for the conditioned stimulus (CS) and a rear panel light for a contextual cue. FG 7142 (8 mg/kg), chlordiazepoxide (CDP, 8 mg/kg), and vehicle were administered i.p. in subsequent extinction sessions. In control animals, operant responding was suppressed during presentation of the CS and contextual cue. The BZR partial inverse agonist FG 7142 exaggerated this suppression,while CDP attenuated it. Lesioned animals were less suppressed than controls across stimulus conditions, with the largest difference between groups observed during presentation of the contextual cue. Presentation of the contextual cue was also associated with a cardioacceleratory response in control animals, and this response was significantly attenuated in lesioned animals. Furthermore, the modulatory effects of BZR ligands on behavioral and autonomic reactions observed in control animals were eliminated in lesioned animals. These data support an important role for cholinergic basal forebrain neurons in the behavioral and autonomic response to anxiety. Funded by HL54428.

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

Schreihofer AM, Guyenet PG (1999) Abolition of cyanide-induced sympathoexcitation by selective lesion of bulbospinal catecholaminergic neurons. Neuroscience 1999 Abstracts 474.6. Society for Neuroscience, MIami, FL.

Summary: The rostral ventrolateral medulla (RVLM) contains BS C1 adrenergic cells and non-CA neurons whose relative importance for the production of sympathetic vasomotor tone and cardiovascular reflexes remains unknown. In the present study we evaluate 2 sympathetic reflexes after selective lesions of BS CA neurons with the neurotoxin saporin-anti-dopamine beta hydroxylase (SAP-DBH). Rats received bilateral microinjections of SAP-DBH (42 ng/200nl/site) into the spinal cord centered at the intermediolateral cell column at T2 & T4 & T6 and were allowed to recover for 3-5 weeks. Arterial pressure (AP), heart rate (HR), and splanchnic nerve activity (SNA) were measured while the rats were chloralose-anesthetized, artificially ventilated, and paralyzed. Baseline AP and HR were comparable between control rats (n-7, 113 +/- 7 mmHg, 426 +/- 12 bpm) and lesioned rats (n=7, 123 +/- 4 mmHg, 448 +/- 7 bpm). In control rats stimulation of the carotid chemoreflex (100 micrograms/kg sodium cyanide, iv) produced a burst in SNA (266 +/- 26%) followed by inhibition (to 18 +/- 3% of base). In contrast, in the SAP-DBH-treated animals cyanide produced only an inhibition of SNA (to 33 +/- 7% of base). Mean AP responses mirrored the SNA responses. In contrast, the Bezold-Jarisch reflex was not diminished in the SAP-DBH-treated rats. Phenyl biguanide (5 micrograms/kg, iv) decreased AP (22 +/- 3 vs. 42 +/- 5 mmHg), SNA (85 +/- 4 vs. 67 +/- 6%), and HR (28 +/- 6 vs. 56 +/- 7 bpm) in control rats and lesioned rats respectively. Histological examination revealed that SAP-DBH depleted the vast majority of BS C1 cells (>70% of the rostral third of the C1 cell group), and >80% of the A5 cell group. These results indicate that sympathetic vasomotor tone persists and rats have a normal mean AP in the absence of most of BS C1 and A5 cells. Although the BS C1 cells may not be required for the Bezold-Jarisch reflex, BS CA cells are essential for the sympathoexcitatory response to cyanide. Work supported by NIH 28785.

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

ATS Poster of the Year Winner

Lin L, Georgievska B, Mattsson A, Isacson O (1999) Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation. Proc Natl Acad Sci U S A 96:12108-12113. doi: 10.1073/pnas.96.21.12108

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

Madden CJ, Ito S, Rinaman L, Wiley RG, Sved AF (1999) Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DBH-saporin. Am J Physiol 46:R1063-R1075. doi: 10.1152/ajpregu.1999.277.4.R1063

Summary: The authors review the use of anti-DBH-SAP (Cat. #IT-03) to study the role of C1 neurons within the rostral ventromedial medulla in cardiovascular regulation. This immunotoxin specifically removes C1 neurons containing dopamine beta-hydroxylase.

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

Chiba AA, Bushnell PJ, Oshiro WM, Gallagher M (1999) Selective removal of cholinergic neurons in the basal forebrain alters cued target detection. Neuroreport 10(14):3119-3123. doi: 10.1097/00001756-199909290-00044

Pizzo DP, Waite JJ, Thal LJ, Winkler J (1999) Intraparenchymal infusions of 192 IgG-saporin: development of a method for selective and discrete lesioning of cholinergic basal forebrain nuclei. J Neurosci Methods 91:9-19. doi: 10.1016/s0165-0270(99)00057-6

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

Gutierrez H, Gutierrez R, Ramirez-Trejo L, Silva-Gandarias R, Ormsby CE, Miranda MI, Bermudez-Rattoni F (1999) Redundant basal forebrain modulation in taste aversion memory formation. J Neurosci 19:7661-7669. doi: 10.1523/JNEUROSCI.19-17-07661.1999

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

Ridley RM, Pugh P, Maclean CJ, Baker HF (1999) Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys. Brain Res 836:120-138. doi: 10.1016/s0006-8993(99)01641-8

Related Products: ME20.4-SAP (Cat. #IT-15)

Gutierrez H, Gutierrez R, Silva-Gandarias R, Estrada J, Miranda MI, Bermudez-Rattoni F (1999) Differential effects of 192 IgG-saporin and NMDA-induced lesions into the basal forebrain on cholinergic activity and taste aversion memory formation. Brain Res 834:136-141. doi: 10.1016/s0006-8993(99)01519-x

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

Basbaum AI (1999) Distinct neurochemical features of acute and persistent pain. Proc Natl Acad Sci U S A 96:7739-7743. doi: 10.1073/pnas.96.14.7739

Related Products: IB4-SAP (Cat. #IT-10)