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The role of orexin in sexual behavior and sexual reward of the male rat

Di Sebastiano AR, Yong-yow S, Coolen LM (2008) The role of orexin in sexual behavior and sexual reward of the male rat. Neuroscience 2008 Abstracts 97.4/UU18. Society for Neuroscience, Washington, DC.

Summary: The hypothalamic neuropeptide orexin has been demonstrated to play a role in reward related to drugs of abuse and is potentially involved in regulation of natural rewarding behaviors. Male sexual behavior has been shown to activate orexin neurons and this behavior is altered by administration of orexin receptor agonists or antagonists. However, the exact role of orexin in male sexual performance, sexual motivation and reward is currently unclear. Therefore, the goal of the current study was to test the hypothesis that orexin plays a critical role in sexual behavior, motivation and reward. First, using Fos as a marker for neural activation, we investigated activation of orexin neurons following different parameters of sexual behavior in sexually naïve and experienced male rats. It was demonstrated that orexin neurons in the lateral hypothalamic area (LHA) and in the dorsal medial hypothalamus/perifornical (PFA-DMH) region become activated with presentation of the female and there is no further increase in activation with other components of mating (15-30% in LHA; 65-80% in PFA-DMH). Next, we tested the functional role of orexin utilizing orexin-cell body specific lesions. Adult male rats underwent lesion or sham surgery using the targeted toxin orexin-saporin or blank-saporin respectively. Following two weeks recovery, sexual behavior was recorded over the course of four mating trials. During the first mating trial, males with complete lesions showed significantly shorter latencies to mount and intromit. This suggests that lesions facilitated sexual performance in naïve animals. This facilitation was attenuated by sexual experience as lesions did not affect any parameter of sexual behavior in experienced animals. Next, runway tests were conducted to determine motivation to run towards a potential partner over two conditioning trials. Lesions did not alter sexual motivation, as lesion and sham males all demonstrated increased speed to run towards an estrous female during the second trial. Finally, a conditioned place preference (CPP) paradigm was conducted as a measure of sexual reward. All groups formed a conditioned preference for the mating-paired chamber, indicating that lesions did not significantly disrupt sexual reward. Overall, these findings suggest that orexin does not play a critical role in male sexual performance, motivation, and reward, however may be involved in general arousal related to sexual behavior.

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

Featured Article: Selective lesions of amygdala intercalated neurons using the Dermorphin-SAP immunotoxin reveal their role in conditioned fear

Likhtik E (2008) Featured Article: Selective lesions of amygdala intercalated neurons using the Dermorphin-SAP immunotoxin reveal their role in conditioned fear. Targeting Trends 9(4)

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

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Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms.

Göz D, Studholme K, Lappi DA, Rollag MD, Provencio I, Morin LP (2008) Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms. PLoS ONE 3(9):e3153. doi: 10.1371/journal.pone.0003153 PMID: 18773079

Summary: Retinal ganglion cells expressing melanopsin photopigment are thought to be involved in non-image forming visual responses to light. The authors had a custom conjugate made between saporin and an anti-melanopsin antibody. A 400-ng injection of the melanopsin-SAP conjugate into the eye of a mouse resulted in a 57% loss of the targeted cells. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data indicates that melanopsin-containing cells are involved in the response to certain non-image forming visual input.

Related Products: Melanopsin-SAP (Cat. #IT-44), Melanopsin Rabbit Polyclonal (Cat. #AB-N38), Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39), Rabbit IgG-SAP (Cat. #IT-35)

Amygdala intercalated neurons are required for expression of fear extinction.

Likhtik E, Popa D, Apergis-Schoute J, Fidacaro GA, Pare D (2008) Amygdala intercalated neurons are required for expression of fear extinction. Nature 454(7204):642-645. doi: 10.1038/nature07167

Summary: Scientists have been using fear learning in animals to study human anxiety disorders. In order to investigate the contribution of amygdala plasticity to fear learning, rats received 0.25-µl bilateral infusions of 3-µM dermorphin-SAP (Cat. #IT-12) into the amygdala. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned rats displayed extinction expression deficits, indicating that the eliminated intercalated amygdala neurons play a large role in the extinction process.

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

Read the featured article in Targeting Trends.

Featured Article: Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress

Radley JJ (2008) Featured Article: Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress. Targeting Trends 9(3)

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

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Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists.

Darmani NA, Wang Y, Abad J, Ray AP, Thrush GR, Ramirez J (2008) Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists. Brain Res 1214:58-72. doi: 10.1016/j.brainres.2008.03.077

Summary: This work investigated the role of central tachykinin NK1 receptors in delayed phase vomiting caused by chemotherapeutics. Least shrews received 1.2 mg/kg intraperitoneal injections of SSP-SAP (Cat. #IT-11). Saporin (Cat. #PR-01) and blank-SAP (Cat. #IT-21) were used as controls. In response to administration of a NK1 receptor agonist lesioned animals vomited less than the control group, indicating an important role for NK1 receptors in emesis.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01), Blank-SAP (Cat. #IT-21)

Hyperphagia and obesity produced by arcuate injection of NPY-saporin do not require upregulation of lateral hypothalamic orexigenic peptide genes.

Li AJ, Dinh TT, Ritter S (2008) Hyperphagia and obesity produced by arcuate injection of NPY-saporin do not require upregulation of lateral hypothalamic orexigenic peptide genes. Peptides 29(10):1732-1739. doi: 10.1016/j.peptides.2008.05.026

Summary: It has already been shown that lesioning NPY receptor-expressing cells in the arcuate nucleus (Arc) and basomedial hypothalamus produces obesity in rats. The authors examined the contribution of orexigenic peptides, orexins, and melanocortin-concentrating hormone to the lesion effects. Rats received bilateral 24 ng injections of NPY-SAP (Cat. #IT-28) into the dorsal border of the Arc. Blank-SAP (Cat. #IT-21) was used as a control. The data suggest that obesity produced by NPY-SAP lesion is different than dietary obesity or obesity associated with leptin or leptin receptor deficiency.

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

Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function.

Li A, Emond L, Nattie E (2008) Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function. (eds. Poulin MJ, Wilson RJA). In: Integration in Respiratory Control. Advances in Experimental Medicine and Biology 605:371-376. Springer, New York, NY. doi: 10.1007/978-0-387-73693-8_65

Summary: The authors examined the role of brainstem catecholamine (CA) neurons in various aspects of breathing and chemoreception. Rats received 5-µg injections of anti-DBH-SAP (Cat. #IT-03) into the 4th ventricle; mouse IgG-SAP (Cat. #IT-18) was used as a control. This method of lesioning left the CA neurons in the peripheral nervous system intact. Lesioned animals displayed a constant decrease in breathing frequency, reduced response to CO2, and increased variability of breathing during REM sleep. Inhibitory cardiovascular effects were also seen.

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

The neonatal injury-induced spinal learning deficit in adult rats: central mechanisms.

Young EE, Baumbauer KM, Hillyer JE, Patterson AM, Hoy KC, Jr., Mintz EM, Joynes RL (2008) The neonatal injury-induced spinal learning deficit in adult rats: central mechanisms. Behav Neurosci 122:589-600. doi: 10.1037/0735-7044.122.3.589

Summary: This report examined whether neonatal injuries had any contralateral effects in adult life, and evaluated the role of the NK1 receptor of adult animals that had been subjected to neonatal trauma. Rats were injected with 5 µl of SP-SAP (Cat. #IT-07, 30 ng/µl, 100 ng/µl, or 300 ng/µl) into the intrathecal space. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate both that injury effects are isolated in the injured limb, and NK1 receptor-expressing cells are involved in processing this pain.

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

Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model.

Siva AC, Wild MA, Kirkland RE, Nolan MJ, Lin B, Maruyama T, Yantiri-Wernimont F, Frederickson S, Bowdish KS, Xin H (2008) Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model. Cancer Res 68:3759-3766. doi: 10.1158/0008-5472.CAN-07-1657

Summary: CUB domain-containing protein 1 (CDCP1) is an antigen expressed on several metastatic cancers, as well as on CD34+ and CD133+ myeloid leukemic blast cells. After demonstrating in vitro activity of the monoclonal antibody 25A11 with Mab-ZAP (Cat. #IT-04) and Hum-ZAP (Cat. #IT-22) the authors had a custom conjugation of 25A11 and saporin made for testing in mice. Goat-IgG-SAP (Cat. #IT-19) was used as a control for in vivo experiments, and saporin (Cat. #PR-01) was the control in vitro. The direct conjugate significantly inhibited tumor growth as well as metastasis in vivo.

Related Products: Mab-ZAP (Cat. #IT-04), Hum-ZAP (Cat. #IT-22), Goat IgG-SAP (Cat. #IT-19), Saporin (Cat #PR-01)

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