Targeting Topics 07q4

Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not in the striatum

Mattsson A, Olson L, Svensson TH, Schilstrom B

Exp Neurol 208(1):73-79, 2007.

Previous data have implicated cholinergic dysfunction in the pathogenesis of schizophrenia. Here the authors investigated whether increased amphetamine-induced release of dopamine was a response to cortical cholinergic denervation. Rats received bilateral 0.067 µg-injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis, and dopamine release was monitored in the nucleus accumbens and striatum. Surprisingly, the increased dopamine release was not linked to loss of cholinergic neurons, but to blocking of muscarinic receptors.

Neonatal basal forebrain cholinergic hypofunction affects ultrasonic vocalizations and fear conditioning responses in preweaning rats

Ricceri L, Cutuli D, Venerosi A, Scattoni ML, Calamandrei G

Behav Brain Res 183(1):111-117, 2007.

In order to expand on previous work investigating the effect of early cholinergic lesions on processing of aversive stimuli the authors administered 0.21 µg of 192-IgG-SAP (Cat. #IT-01) into the third ventricle of 7 day-old rat pups. One unexpected result in lesioned animals was the enhancement of fear-conditioned responses that are dependent on the hippocampus. The authors discuss several theories addressing the implications of these data.

Ketanserin-induced baroreflex enhancement in spontaneously hypertensive rats depends on central 5-HT(2A) receptors

Shen FM, Wang J, Ni CR, Yu JG, Wang WZ, Su DF

Clin Exp Pharmacol Physiol 34(8):702-707, 2007.

Ketanserin is an antihypertensive drug that effectively lowers blood pressure, decreases blood pressure variability, and enhances blood pressure response in spontaneously hypertensive rats. Using the fact that ketanserin is a selective 5-HT2A antagonist, the authors investigated which of these effects utilized the 5-HT2A receptor. Following a 5-nmol ventricular injection of anti-SERT-SAP (Cat. #IT-23) the blood pressure parameters modified by ketanserin were monitored. The data suggest that the baroreflex sensitivity-enhancing effects of ketanserin use the 5-HT2A pathway, but antihypertensive effects follow a different route.

Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride

Rinaman L, Dzmura V

Am J Physiol Regul Integr Comp Physiol 293(4):R1495-1503, 2007.

Lithium chloride (LiCl) is frequently used to study neural attributes of “sickness behavior.” Previous work by these authors showed that noradrenergic neurons in the nucleus of the solitary tract (NST) are involved in the inhibition of food uptake by cholecystokinin. Here, 20 ng total of anti-DBH-SAP (Cat. #IT-03) was injected into the NST of rats. Lesioned animals demonstrated significantly reduced inhibition of food intake in response to LiCl, but conditioned flavor avoidance was left intact.

Selective hippocampal cholinergic deafferentation impairs self-movement cue use during a food hoarding task

Martin MM, Wallace DG

Behav Brain Res 183(1):78-86, 2007.

There are conflicting data surrounding the role of the septohippocampal system in spatial orientation. The authors suggest that the presence of spatial clues during some of these tests may skew those results. Rats were injected with a total of 0.35 µg of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Lesioned animals had more difficulty navigating by self-movement cues, but the ability to use environmental cues was left intact. These experiments demonstrate that rats can use environmental information to compensate for loss of circuits that analyze self-movement.

Behavioral and immunohistological effects of cholinergic damage in immunolesioned rats: Alteration of c-Fos and polysialylated neural cell adhesion molecule expression

Chambon C, Paban V, Manrique C, Alescio-Lautier B

Neuroscience 147(4):893-905, 2007.

In this work the authors looked to expand the knowledge of molecular events and brain structure changes following cholinergic immunolesion. Rats were treated with bilateral injections of 192-IgG-SAP (Cat. #IT-01); 37.5 ng per side into the medial septum, and 75 ng per side into the nucleus basalis magnocellularis. One month after treatment behavioral deficits were drastic and cholinergic neurons had completely disappeared. Elevated levels of polysialylated neural cell adhesion molecule were temporarily able to compensate for the loss of cholinergic neurons.

Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections

Gibbs RB

Horm Behav 52(3):352-359, 2007.

Estradiol appears to enhance cholinergic projections to the hippocampus and frontal cortex as shown by tests of response patterns and strategy in rats. The author tested whether this effect was involved with turning strategy, defined as which arm was chosen first in a T-maze. 0.22 µg injections of 192-IgG-SAP (Cat. #IT-01) were made into the medial septum of rats. Lesioned animals utilized a persistent turning strategy; they always chose the same arm of the maze first, even after the administration of estradiol. These data suggest that although the effects of estradiol are not linked to turning strategy, estradiol does interact with the cholinergic system.

Sensory experience determines enrichment-induced plasticity in rat auditory cortex

Percaccio CR, Pruette AL, Mistry ST, Chen YH, Kilgard MP

Brain Res 1174:76-91, 2007.

Animals housed in enriched environments display numerous signs of good neural health. In this work the authors examined the role acetylcholine plays in this plasticity. 2.6 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the left lateral ventricle of rats. Auditory-evoked responses were used to assess the effect of lesioning cholinergic neurons. Response strength was not reduced in lesioned animals, indicating that cholinergic deficits do not affect this system.

Induction and survival of binucleated Purkinje neurons by selective damage and aging

Magrassi L, Grimaldi P, Ibatici A, Corselli M, Ciardelli L, Castello S, Podesta M, Frassoni F, Rossi F

J Neurosci 27(37):9885-9892, 2007.

Donor bone marrow-derived cells are thought to fuse with host Purkinje cells in small numbers to create binucleated cells. These fusions have been found to persist within the recipient for long periods of time. The authors injected 2.2 µg of 192-IgG-SAP (Cat. #IT-01) into the right lateral ventricle of rats to examine whether the damage of host Purkinje cells is a method to increase the numbers of binucleated cells. The data suggest an alternate method is present for the creation of these cells.

Raphe Magnus Nucleus is involved in ventilatory but not hypothermic response to CO2

Dias MB, Nucci TB, Margatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG

J Appl Physiol 103(5):1780-1788, 2007.

In this work the authors investigated the role that serotonergic neurons in the Raphe Magnus Nucleus (RMg) play in ventilatory and thermal responses to hypercapnia. 0.1 µl of 1 µM anti-SERT-SAP (Cat. #IT-23) was injected into the RMg of rats. Mouse-IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals had a decreased ventilatory response to CO2, but hypercapnia-induced hypothermia was not affected. The data indicate that RMg serotonergic neurons contribute to CO2 ventilatory response but not to maintenance of ventilation.

A limited role for microglia in antibody mediated plaque clearance in APP mice

Garcia-Alloza M, Ferrara BJ, Dodwell SA, Hickey GA, Hyman BT, Bacskai BJ

Neurobiol Dis 28(3):286-292, 2007.

Microglia are thought to play a key role in the clearance of amyloid-beta (Abeta) in Alzheimer’s disease. To examine this role the authors applied 30 µl of 0.5 mg/ml Mac-1-SAP (Cat. #IT-06) to the brain surface of mice for 20 minutes. The number of microglia and plaques was determined by counting of immunohistochemical samples. Results indicate that microglia play a minor role in clearing Abeta plaques, although the interaction of microglia-mediated inflammation and anti-Abeta antibodies appears to be vital in this process.