Targeting Topics 02q3

Impairments in negative patterning, but not simple discrimination learning, in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis.

Butt AE, Noble MM, Rogers JL, Rea TE.

Behav Neurosci 116(2):241-255, 2002. PMID: 11996310

192-Saporin (Cat. #IT-01) administration to the basal forebrain has frequently been used in rats to create a model for Alzheimer’s disease. The authors used 0.2 μl bilateral injections of 0.4 μg/μl 192- SAP into the nucleus basalis magnocellularis (NBM). Previous studies using non-specific excitotoxic agents have suggested the involvement of the NBM in learning and memory. The authors confirm more recent findings that indicate some of the deficits produced by these excitotoxins are due to the non- specific lesioning caused by these agents. The highly selective cholinergic lesioning produced by 192-Saporin left simple association learning intact but impaired more complicated configural association processes.

Alpha-7 nicotinic receptor expression by two distinct cell types in the dorsal raphe nucleus and locus coeruleus of rat.

Bitner RS, Nikkel AL.

Brain Res 938(1-2):45-54, 2002. PMID: 12031534

Neuronal nicotinic acetylcholine receptors (nAChRs) are suspected to play a role in neurophysiological disorders such as schizophrenia, Alzheimer’s disease, and epilepsy. Whereas the molecular and cellular properties of these receptors have been well characterized, the role of nAChRs in the nervous system is as yet unclear. The authors injected rats intracerebroventricularly with 5 μg/5 μl of anti-DBH-SAP (Cat. #IT-03) to eliminate the noradrenergic nuclei. Using these data along with data acquired by elimination of serotonergic nuclei with 5,7-DHT, the authors showed that both noradrenergic nuclei in the locus coeruleus and serotonergic nuclei in the dorsal raphe nucleus express the alpha-7 nAChR subunit.

Depressor and tachypneic responses to chemical stimulation of the ventral respiratory group are reduced by ablation of neurokinin-1 receptor-expressing neurons.

Wang H, Germanson TP, Guyenet PG.

J Neurosci 22(9):3755-3764, 2002. PMID: 11978851

The pre-Bötzinger complex is a region of the ventral respiratory group (VRG) in the brain. Injection of excitatory amino acids into this region can cause a variety of responses such as rapid breathing, hypotension, and elevated arterial pressure. The authors used SSP-SAP (Cat. #IT-11) to eliminate the neurokinin-1 receptor (NK-1r) positive neurons in the VRG to determine their role in control of respiration and arterial pressure. Intraparenchymal injection of 0.313 ng/50 nl SSP-SAP produced several abnormal respiratory effects in rats treated with excitatory amino acids. The results indicate that NK-1r positive neurons in the ventrolateral medulla play an important role in respiratory rhythm and blood pressure.

Interactions between aging and cortical cholinergic deafferentation on attention.

Burk JA, Herzog CD, Porter MC, Sarter M.

Neurobiol Aging 23(3):467-477, 2002. PMID: 11959409

Trauma to forebrain cholinergic neurons is suspected to make these neurons more susceptible to future age-related loss of function. The authors tested this theory by making incomplete lesions of the basal forebrain cholinergic system using bilateral infusions of 192-Saporin (0.5 μl of 0.15 μg/μl, Cat. #IT-01) in rats trained prior to surgery. The attentional performance of the treated rats did not differ from control animals until the age of 31 months. The data indicate that pre-existing damage to the cholinergic basal forebrain region yields age-related attentional impairments.

Selective behavioral and neurochemical effects of cholinergic lesions produced by intrabasalis infusions of 192 IgG-saporin on attentional performance in a five-choice serial reaction time task.

McGaughy J, Dalley JW, Morrison CH, Everitt BJ, Robbins TW.

J Neurosci 22(5):1905-1913, 2002. PMID: 11880520

192-Saporin (Cat. #IT-01) has been a very useful tool in determining the role of the basal forebrain cholinergic system in arousal and attention tasks. The authors lesioned the nucleus basalis magnocellularis of rats with an infusion of 0.5 μl per hemisphere of 0.15 μg/μl or 0.45 μg/μl 192- Saporin. The data show a correlation between the extent of the lesion and the amount of impairment in an attentional task. The authors also found that the accuracy deficits in the task could be ameliorated by lengthening the stimulus time, or exacerbated by increasing the event rate. Taken together the data indicate a direct relationship between basal forebrain damage and impaired attentional function.

Septal grafts and evoked acetylcholine release in the rat hippocampus after 192 IgG-saporin lesions.

Birthelmer A, Dommes E, Jeltsch H, Cassel JC, Jackisch R.

Neuroreport 13(7):973-976, 2002. PMID: 12004202

The authors investigate the structural and behavioral effects of intrahippocampal grafts containing cholinergic neurons into a lesioned region of the brain. Previous studies in rats were complicated by the lack of a specific cholinergic lesioning agent. 0.4 μg 192-Saporin (Cat. #IT-01) in 0.4 μl was injected into the vertical limb of the diagonal band of Broca in rats, then 6 to 10 months later the animals received intrahippocampal grafts of septal cells containing cholinergic neurons. Measurement of noradrenaline and serotonin uptake indicate that the grafts were able to produce only modest cholinergic effects. The authors conclude that this may be a result of performing the graft too soon following administration of the immunotoxin.

Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain.

Burgess SE, Gardell LR, Ossipov MH, Malan TPJ, Vanderah TW, Lai J, Porreca F.

J Neurosci 22(12):5129-5136, 2002. PMID: 12077208

Various indications, such as declining afferent discharge over time, suggest that the mechanisms involved in persistent neuropathic pain are different than those that initiate the pain. The authors have previously shown that cells expressing the mu- opioid receptor are involved in the descending pain pathway. In this work, the authors lesioned the rostral ventromedial medulla (RVM) in rats using 1.5 pmol in 0.5 μl of dermorphin-SAP (Cat. #IT-12) administered to each side of the RVM. Measurements of pain-related behavior show that mu-opioid receptor-expressing cells in the RVM are involved in the maintenance of heightened sensitivity to stimuli seen in neuropathic pain.