Targeting Topics 02q1

Colocalization of mu-opioid receptors and activated G-proteins in rat cingulate cortex.

Vogt LJ, Sim-Selley LJ, Childers SR, Wiley RG, Vogt BA.

J Pharmacol Exp Ther 299(3):840-848, 2001. PMID: 11714867

The anterior cingulate cortex (ACC) is a primary site of opiate drug action, and much of this activity is associated with the μ-opioid receptor (MOR). The mechanisms by which MOR regulates pain in the ACC are not well understood. Using anti- DBH-SAP (7 μg into left lateral ventricle in rat; Cat. #IT-03) the authors mapped MOR activity in the ACC and evaluated the histochemical and behavioral relationships between MOR binding and μ-receptor- activated G-proteins after lesioning.

Selective immunolesions of cholinergic neurons in mice: effects on neuroanatomy, neurochemistry, and behavior.

Berger-Sweeney J, Stearns NA, Murg SL, Floerke-Nashner LR, Lappi DA, Baxter MG.

J Neurosci 21(20):8164-8173, 2001. PMID: 11588189

192-Saporin (Cat. #IT-01) has long been an effective agent for elimination of cholinergic neurons in the basal forebrain of rats. Until the development of mu p75-SAP (Cat. #IT-16) there was no equivalent agent for use in mice. The authors tested mu p75-SAP in vitro and in vivo (1.8-3.6 μg in right lateral ventricle), using cytotoxic, histochemical, and behavioral assays. The data shows that mu p75-SAP is a highly selective and efficacious lesioning agent for cholinergic neurons in the mouse. The authors conclude that mu p75- SAP will be a powerful tool to use in combination with genetic modification to investigate cholinergic damage in mouse models of Alzheimer’s disease.

Extensive immunolesions of basal forebrain cholinergic system impair offspring recognition in sheep.

Ferreira G, Meurisse M, Gervais R, Ravel N, Levy F.

Neuroscience 106(1):103-116, 2001. PMID: 11564421

Through the use of 192-Saporin (Cat. #IT-01) the association of basal forebrain cholinergic neurons to learning instrumental tasks has been well established in the rat. The authors wished to examine whether these neurons were also associated with social learning tasks, such as offspring recognition in sheep. Using ME20.4-SAP (Cat. #IT-15) the basal forebrain cholinergic neurons of sheep were lesioned by intraventricular bilateral injections (150 μg). The results demonstrate that these neurons contribute to visual discrimination learning, and are involved in formation of lamb recognition memory.

Dissociation between the attentional functions mediated via basal forebrain cholinergic and GABAergic neurons.

Burk JA, Sarter M.

Neuroscience 105(4):899-909, 2001. PMID: 11530228

The specificity and efficacy of 192-Saporin (Cat. #IT-01) has allowed the extensive investigation of cortical cholinergic inputs in attentional functions. Little is known about the function of non-cholinergic neurons because of the lack of a specific tool to eliminate these projections. The authors injected 192-Saporin (0.1 μg/0.5 μl bilateral infusions) into rats and compared performance to rats treated with ibotenic acid to eliminate GABAergic neurons in attention performance tasks. While the ibotenic acid lesions were not as specific as those produced by 192-Saporin, the data suggest a role for the basal forebrain GABAergic neurons in attentional functions.

Novel method for localized, functional sympathetic nervous system denervation of peripheral tissue using guanethidine.

Demas GE, Bartness TJ.

J Neurosci Methods 112(1):21-28, 2001. PMID: 11640954

Sympathectomy, or surgical interruption of sympathetic nerve pathways, is an important technique in the analysis of the sympathetic nervous system. The authors investigate and compare several different methods of performing a sympathectomy in hamsters, including surgery, chemical, and immunotoxic lesions using anti- DBH-SAP (ten 2-μl injections, at either 0.65 μg/μl or 0.325 μg/μl, into inguinal white adipose tissue; Cat. #IT-03).

Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn’s disease.

Kanai T, Watanabe M, Okazawa A, Sato T, Yamazaki M, Okamoto S, Ishii H, Totsuka T, Iiyama R, Okamoto R, Ikeda M, Kurimoto M, Takeda K, Akira S, Hibi T.

Gastroenterology 121(4):875-888, 2001. PMID: 11606501

Crohn’s disease is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of cytokines that are responsible for inflammation. The authors investigated the role of these macrophages in a mouse model by eliminating them with Mac-1-SAP (20 μg parenterally in tail vein; Cat. #IT-06). Seven days after treatment, mice showed no evidence of intestinal inflammation. These data demonstrate the role of macrophages in the development of inflammatory bowel conditions.

The effects of manipulations of attentional demand on cortical acetylcholine release.

Himmelheber AM, Sarter M, Bruno JP.

Brain Res Cogn Brain Res 12(3):353-370, 2001. PMID: 11689296

Cortical cholinergic afferents from the basal forebrain are suspected to be involved in attentional tasks. Regulatory impairment of these afferents has been hypothesized to contribute to attentional deficits seen in conditions as diverse as Alzheimer’s disease and schizophrenia. The authors have previously shown that 192-Saporin (Cat. #IT-01) lesions result in severe impairments in tasks requiring sustained attentional processing. In these experiments the authors suggest that cell response is dependent on the level of demand. They demonstrate that removal of p75+ cells (0.5 μg/μl bilaterally infused into the nucleus basalis region in rat) impairs sustained attentional performance, but does not impact low-demand task performance.

Long-term intrathecal catheterization in the rat.

Jasmin L, Ohara PT.

J Neurosci Methods 110(1-2):81-89, 2001. PMID: 11564527

The authors have developed a method that allows repeated administration of drugs with minimal stress to an experimental animal. To test the efficacy of this intrathecal catheter, they injected anti-DBH-SAP (5 μg; Cat. #IT-03) and investigated the noradrenergic denervation of the spinal cord. All animals treated with anti-DBH-SAP showed extensive loss of spinal noradrenergic ennervation. Even three months after catheter implantation, the elimination of noradrenergic neurons in the spinal cord could be produced. This indicates the intrathecal catheter is an effective tool for the study of multiple-dose drug delivery.

Differential changes in rat cholinergic parameters subsequent to immunotoxic lesion of the basal forebrain nuclei.

Waite JJ, Chen AD.

Brain Res 918(1-2):113-120, 2001. PMID: 11684049

192-Saporin (Cat. #IT-01) is used extensively to eliminate the cholinergic neurons of the basal forebrain in rats. Waite and Chen compare the degree of loss between 192-Saporin (6 or 8.2 μg in 10 μl into left lateral ventricle) and control (Saporin, 1.82 μg into left lateral ventricle; Cat. #PR-01) using three methods: Assay of post mortem choline acetyltransferase activity, in vivo microdialysis of extracellular acetylcholine (ACh), and in vivo assessment of the rate of ACh synthesis. The infusion of saporin alone had no effect. After fifteen weeks, the authors report compensation of cholinergic activity in lesioned animals occurs in the hippocampus, but not in the frontal cortex as determined by measurement of the rate of ACh synthesis.