targeted-toxins

Butt AE, Noble MM, Rogers JL, Rea TE (2002) Impairments in negative patterning, but not simple discrimination learning, in rats with 192 IgG-Saporin lesions of the nucleus basalis magnocellularis. Behav Neurosci 116(2):241-255. doi: 10.1037//0735-7044.116.2.241

Summary: 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.

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

Blanco-Centurion C (2002) Featured Article: HCRT-SAP lesion produces sleepiness while anti-DBH-SAP lesion does not. Targeting Trends 3(2)

Related Products: Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)

Read the featured article in Targeting Trends.

See Also:

• Blanco-Centurion CA et al. Hypocretin B-Saporin Lesions Of The Brainstem Increase Rem Sleep At Night. Neuroscience 2001 Abstracts 410.9, 2001. Society for Neuroscience, San Diego, CA

Butt AE, Bowman TD (2002) Transverse patterning reveals a dissociation of simple and configural association learning abilities in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis. Neurobiol Learn Mem 77:211-233. doi: 10.1006/nlme.2001.4013

Summary: Using 80 ng bilateral infusions of 192-Saporin (Cat. #IT-01) into each of the medial and lateral target sites of the nucleus basalis magnocellularis (NBM) in rats, the authors demonstrate that lesioning the cholinergic systems of the NBM impairs a more complicated learning technique, while leaving simple association learning intact. The results also show that the transition between these two learning strategies is impaired in lesioned animals.

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

Mattsson A, Ögren SO, Olson L (2002) Facilitation of dopamine-mediated locomotor activity in adult rats following cholinergic denervation. Exp Neurol 174:96-108. doi: 10.1006/exnr.2001.7850

Summary: Using 80 ng bilateral infusions of 192-Saporin (Cat. #IT-01) into each of the medial and lateral target sites of the nucleus basalis magnocellularis (NBM) in rats, the authors demonstrate that lesioning the cholinergic systems of the NBM impairs a more complicated learning technique, while leaving simple association learning intact. The results also show that the transition between these two learning strategies is impaired in lesioned animals.

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

McGaughy J, Dalley JW, Morrison CH, Everitt BJ, Robbins TW (2002) 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. J Neurosci 22(5):1905-1913. doi: 10.1523/JNEUROSCI.22-05-01905.2002

Summary: 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.

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

Power AE, Thal LJ, McGaugh JL (2002) Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala. Proc Natl Acad Sci U S A 99(4):2315-2319. doi: 10.1073/pnas.022627799

Summary: There is evidence that memory consolidation (retention) can be modulated by drugs and stress hormones acting in the basolateral amygdala (BLA). The BLA sends projections to the nucleus basalis magnocellularis (NBM), which in turn sends cholinergic projections to the neocortex. The authors used 100 ng bilateral infusions of 192-Saporin (Cat. #IT-01) in 500 nl 0.1 M PBS to investigate whether lesions of the cholinergic NBM projections affect BLA modulation of memory. 192-Saporin lesions blocked memory enhancement normally induced by norepinephrine infusions into the BLA. This finding suggests NBM-cortex projections may mediate BLA modulation of memory storage or processing in the neocortex.

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

Kingery WS, Agashe GS, Guo TZ, Sawamura S, Davies MF, Clark JD, Kobilka BK, Maze M (2002) Isoflurane and nociception: Spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception. Anesthesiol 96:367-374. doi: 10.1097/00000542-200202000-00023

Summary: The authors injected 3 µg/3 µl of anti-DBH-SAP (Cat. #IT-03) into the lateral ventricle of rats to determine whether noradrenergic brainstem nuclei and descending spinal pathways are responsible for the antinociceptive actions of isoflurane. The results indicate that isoflurane modulates nociception by as many as three mechanisms, utilizing various combinations of noradrenergic neurons, adrenoceptors, and descending spinal pathways.

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

Safety Instructions

Good laboratory technique must be employed for the safe handling of this product. This requires observation of the following practices:

1. Wear appropriate laboratory attire, including lab coat, gloves and safety glasses.

2. Do not pipet by mouth, inhale, ingest or allow product to come into contact with open wounds. Wash thoroughly any part of the body which comes into contact with the product.

3. Avoid accidental autoinjection by exercising extreme care when handling in conjunction with any injection device.

4. This product is intended for research use by qualified personnel only. It is not intended for use in humans or as a diagnostic agent. Advanced Targeting Systems is not liable for any damages resulting from the misuse or handling of this product.

For disposal: autoclave, or expose to 0.2 M NaOH, materials that come into contact with the toxin.

Q: We’re submitting a protocol to our IACUC to use IB4-SAP (Cat. #IT-10). We plan to inject the targeted toxin and then sacrifice the animal ten days later. What, if any, are the safety issues here?

A: The only danger to lab personnel from IB4-SAP would be accidental self-injection, and even then, at the doses typically used in rats, it would only produce very localized effects at the injection site.

Once injected into animals, the agent is rapidly rendered inaccessible to anyone else by binding, internalization and eventual catabolism. It is extremely unlikely that intact toxin would ever be excreted or recoverable from the rats. The components of the toxin, IB4 and saporin, by themselves are no toxic threat. We use no special precautions with such rats except appropriate care for whatever neurologic deficits they develop, i.e. foot drop, autotomy, etc.

One caveat: To the best of my knowledge the above statements are accurate, but I do not know of any experimental data that directly addresses the issues. I base my comments on our long experience with similar agents including ricin and volkensin which are much more toxic and unstable.

See: Targeted Toxins

Cahill JFX, Baxter MG (2001) Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning. Eur J Neurosci 14:1856-1864. doi: 10.1046/j.0953-816x.2001.01807.x

Summary: The authors compared ibotenic acid (IA)-treated rats with those injected with 45 ng and 30 ng of 192-Saporin (Cat. #IT-01) into two separate coordinates of the medial septum/vertical limb of the diagonal band (MS/VDB) to investigate the role of basal forebrain projections in modulating strategy selection in spatial learning. While rats with IA lesions in the MS/VDB demonstrated significant disruption of the learning process, the 192-Saporin-lesioned rats did not show this effect.

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

Lamprea MR, Cardenas FP, Silveira R, Morato S, Walsh TJ (2000) Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: Forebrain cholinergic mechanisms. Behav Brain Res 117:97-105. doi: 10.1016/s0166-4328(00)00294-1

Summary: The septo-hippocampal pathway has been implicated in many behavioral processes such as learning, anxiety, and motivation. Using 192-Saporin (Cat. #IT-01) to lesion the cholinergic neurons of the medial septum of rats, the authors demonstrate changes in exploratory behavior associated with learning, but no changes in anxiety-associated behavior in their elevated plus maze paradigm.

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