control-conjugates

Kline IV RH, Wiley RG (2008) Spinal mu-opioid receptor-expressing dorsal horn neurons: role in nociception and morphine antinociception. J Neurosci 28:904-913. doi: 10.1523/JNEUROSCI.4452-07.2008

Summary: The authors used Dermorphin-SAP (Cat. #IT-12) to investigate the function of spinal cord mu-opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia. Rats were treated with 500 ng intrathecal injections of Dermorphin-SAP; 500 ng of Blank-SAP (Cat. #IT-21), and up to 1 µg of Saporin (Cat. #PR-01) were used as controls. The data indicate that MOR-expressing dorsal horn neurons are necessary for morphine action and play a role in nocifensive responses to persistent pain in the formalin test.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21), Saporin (Cat. #PR-01)

Berdiev RK, Chepurnov SA, Veening JG, Chepurnova NE, van Luijtelaar G (2007) The role of the nucleus basalis of Meynert and reticular thalamic nucleus in pathogenesis of genetically determined absence epilepsy in rats: A lesion study. Brain Res 1185:266-274. doi: 10.1016/j.brainres.2007.09.010

Summary: Absence seizures due to epilepsy usually occur during passive behavior. This work investigated the role of the cholinergic nucleus basalis of Meynert (NB) and the reticular thalamic nucleus (RT) in these seizures. Rats received either 75 ng of 192-IgG-SAP (Cat. #IT-01) or the control, mouse IgG-SAP (Cat. #IT-18), into the NB and the RT. Loss of cholinergic neurons in the NB resulted in an increased number of spike-and-wave discharges, a marker for absence seizures.

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)

Shank EJ, Seitz PK, Bubar MJ, Stutz SJ, Cunningham KA (2007) Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity. Behav Neurosci 121:1224-1233. doi: 10.1037/0735-7044.121.6.1224

Summary: To further examine the importance of the ventral tegmental area (VTA) g-aminobutyric acid (GABA) neurons in behavioral function, the authors lesioned the VTA of rats with dermorphin-saporin (Cat. #IT-12). Lesioned animals received 1 or 2 pmol/200 nl bilateral injections of conjugate; blank-SAP (Cat. #IT-21) was used as a control. Rats treated with dermorphin-SAP displayed significantly elevated motility as compared to control animals. Rats receiving 1 pmol of dermorphin-SAP returned to normal motility 14 days after treatment, but rats receiving 2 pmol maintained the increased motility through day 14.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Likhtik E, Popa D, Apergis-Schoute J, Fidacaro GA, Pare D (2007) Lesion of intercalated (ITC) amygdala neurons interfere with extinction of classically conditioned fear responses. Neuroscience 2007 Abstracts 426.6/HHH29. Society for Neuroscience, San Diego, CA.

Summary: The acquisition of conditioned fear responses (CRs) is thought to involve the potentiation of synapses conveying information about the conditioned stimulus (CS) to the basolateral (BLA) amygdala. Expression of CRs would depend on the transfer of potentiated CS inputs by the BLA to the central amygdala (CE). In contrast, the mechanisms of extinction remain controversial. It has been proposed that ITC neurons, which receive BLA inputs and generate feedforward inhibition in CE, are in a key position to mediate extinction. In this view, NMDA-dependent potentiation of BLA inputs to ITC cells during extinction training, would dampen the impact of CS-related BLA activity on CE neurons, inhibiting CRs. However, this idea is difficult to test because ITC cells occur in small, lateromedially dispersed clusters, making conventional lesioning methods inadequate. Here, we took advantage of the fact that, compared to the rest of the amygdala, ITC cells express a much higher concentration of mu opioid receptors (muORs). As a result, we could lesion them by performing local injections of a peptide-toxin conjugate (demorphin conjugated to saporin, D-Sap) that selectively targets cells expressing muORs. Control rats received injections of saporin conjugated to a blank peptide (B-Sap). On Day 1, intact rats were subjected to a standard cued fear conditioning protocol in context A. On Day 2, they received 20 CS alone presentations in a different context (B). On Day 3, rats then received either D-Sap or B-Sap injections in the ITC cell masses. One week later, extinction recall was tested in context B with 10 CS alone presentations. Compared to control (B-Sap) rats (n=10), ITC-lesioned rats (n=5) had an extinction deficit (ANOVA, F=11.687, p = 0.005). Post-hoc t-tests comparing % time freezing during the first five or last five CSs revealed that rats with ITC lesions had significantly higher freezing levels throughout the extinction recall test (p<0.002 for both tests). These differences were not attributable to a non-specific increase in freezing or anxiety levels as exploratory behaviors in a novel open field in control and ITC-lesioned rats were indistinguishable. Overall, these results indicate that ITC cells are involved in the expression of extinction.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Li A-J, Dinh TT, Ritter S (2007) Destruction of NPY receptor expressing neurons in the arcuate nucleus causes obesity and hyperphagia without increasing lateral hypothalamic orexigenic peptide gene expression. Neuroscience 2007 Abstracts 524.20/BBB20. Society for Neuroscience, San Diego, CA.

Summary: NPY-SAP, a conjugate of neuropeptide Y (NPY) and the ribosomal inactivating toxin, saporin (SAP), is a compound that selectively lesions NPY receptor-expressing neurons. Previously we showed that injection of NPY-SAP into the hypothalamic arcuate nucleus (ARC) induces hyperphagia and obesity in rats. To further investigate the mechanisms responsible for NPY-SAP-induced obesity, we injected NPY-SAP or blank-saporin (B-SAP) control into the ARC and subsequently examined the expression of two orexigenic neuropeptide genes in the lateral hypothalamic area (LHA), which is densely innervated by ARC neurons. Our hypothesis was that loss of leptin-sensitive neurons in the ARC in the NPY-SAP injected rats would lead to increased expression of orexigenic neurons elsewhere in the hypothalamic feeding circuitry. Body weight gain and food intake were dramatically increased in the NPY-SAP group. In addition, expression of NPY and cocaine- and amphetamine-regulated transcript (CART) mRNA was significantly reduced in the ARC of obese rats, indicating a loss of NPY receptor-expressing NPY and CART neurons in this region. In contrast, NPY and CART gene expression in the dorsomedial hypothalamic nucleus was unchanged in NPY-SAP rats, indicating that the NPY-SAP-induced lesion was limited to the ARC. However, contrary to our hypothesis, expression of the orexigenic neuronpeptides, melanin-concentrating hormone (MCH) or prepro-orexin mRNA in LHA was not enhanced, but was slightly reduced in the NPY-SAP rats. These results indicate that an enhancement of MCH or orexin expression in the LHA is not necessary for the hyperphagia and obesity observed after NPY-SAP lesions in the ARC. Supported by PHS grant #DK 40498.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Dias MB, Nucci TB, Margatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG (2007) Raphe Magnus Nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol 103(5):1780-1788. doi: 10.1152/japplphysiol.00424.2007

Summary: 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.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502:455-467. doi: 10.1002/cne.21329

Summary: Interleukin-1 (IL-1) is one of the cytokines that mediates interactions between the immune system and the central nervous system. 380-ng injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus (PVH) of rats. Saporin (Cat. #PR-01) and mouse IgG-SAP (Cat. #IT-18) were used as controls. Lesioned animals demonstrated reduced responses to administration of IL-1, but restraint stress responses were left intact. The data suggest that ascending catecholaminergic projections mediate PVH response to IL-1.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01), Mouse IgG-SAP (Cat. #IT-18)

Truitt WA, Sajdyk TJ, Dietrich AD, Oberlin B, McDougle CJ, Shekhar A (2007) From anxiety to autism: spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats. Psychopharmacology (Berl) 191(1):107-118. doi: 10.1007/s00213-006-0674-y

Summary: The amygdala has been identified as being involved in social behaviors. Six 4 ng injections of SSP-SAP (Cat. #IT-11) were administered bilaterally into the basolateral nucleus (BLA) of the amygdala of rats. Blank-SAP (Cat. #IT-21) was used as a control. Results of a social interaction paradigm suggest that in normal animals social inhibition can be overcome by habituation. In lesioned animals, however, social inhibition is not reversed by habituation, indicating that NK-1 receptor-expressing GABAergic interneurons in the BLA are important in this system.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Furlong T, Carrive P (2007) Neurotoxic lesions centered on the perifornical hypothalamus abolish the cardiovascular and behavioral responses of conditioned fear to context but not of restraint. Brain Res 1128(1):107-119. doi: 10.1016/j.brainres.2006.10.058

Summary: This work examined the role of orexin-containing neurons in the perifornical hypothalamus (PeF) during stress response. Orexin-SAP (Cat. #IT-20) or the control conjugate blank-SAP (Cat. #IT-21) was injected into the PeF of pre-conditioned rats. Tests measuring restraint and conditioned fear to context were then performed on the lesioned animals. While the lesioning was not specific enough to connect results to orexin-containing neurons, the data indicate that the PeF is critical for some forms of stress, but not others.

Related Products: Orexin-B-SAP (Cat. #IT-20), Blank-SAP (Cat. #IT-21)

Masawaki A, Sugiyo S, Shimoda T, Sakai Y, Watanabe M, Moritani M, Yoshida A, Niwa H, Takemura M (2006) Formalin-induced pain-related responses in rat lacking neurokinin-1 receptor neurons in the trigeminal nucleus caudalis. Neuroscience 2006 Abstracts 50.8. Society for Neuroscience, Atlanta, GA.

Summary: This study examines the effect of intra cisterna magna injection of substance P (SP) conjugated to saporin (SP-Sap; 5µM, 5µl) on formalin-induced pain-related behavior (PRB; face scrubbing behavior ) and c-Fos expression in the trigeminal nucleus caudalis (SpVc). In SP-Sap-treated rats, the numbers of NK-1-immunoreactive neurons in lamina I of the SpVc decreased compared with those in saline- or blank Sap-treated rats. The mean numbers ±SEM of PRB /5 min at the first phase (0-5 min after For injection) were 58.2±19.2 in the SP-Sap-treated rats, 115.6±14.0 in the saline treated rats and 86.9±45.7 in the blank-Sap-treated rats. The numbers at the quiescent period (5-10 min) were 45.2±26.3 in the SP-Sap- treated rats, 93.6±26.5 in the saline treated rats and 69.4±16.3 in the blank-Sap-treated rats. These at the former second phase (10-50 min) were 58.1±22.3 in the SP-Sap-treated rats, 133.6±26.1 in the saline treated rats and 95.8±29.6in the blank-Sap-treated rats. These at the latter second phase (55-90 min) were 7.0±5.6 in the SP-Sap-treated rats,13.7±12.4 in the saline treated rats and 10.4±22.5 in the blank-Sap-treated rats. These results indicate that formalin-induced nociceptive responses in the SP-Sap-treated rats are reduced.

Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)