sfn2005

Coolen LM, Amstalden KAZ, Allard J (2005) Involvement of lumbar spinothalamic cells in relay of sensory cues related to vaginocervical stimulation in female rats. Neuroscience 2005 Abstracts 321.13. Society for Neuroscience, Washington, DC.

Summary: The rat lumbar spinal cord contains a population of galanin containing spinothalamic (LSt) cells, which in male rats play a pivotal role in the control of ejaculation. However, the function of LSt cells in female rats is unknown. LSt cells project to the parvocellular subparafascicular thalamic nucleus (SPFp), where Fos is expressed following vaginocervical stimulation (VCS). Hence, we hypothesize that LSt cells are involved in relay of sensory cues related to VCS to the brain. To test this hypothesis, the effects of LSt lesions were investigated on two parameters that are dependent on relay of VCS-related cues: pseudopregancy and Fos expression in the SPFp. Adult female Sprague Dawley rats received infusions of substance P-conjugated (SSP-SAP) or unconjugated saporin (control) in lumbar levels 3-4. Females were investigated for: estrous cyclicity, expression of sexual behavior, and induction of pseudopregnancy by mating with vasectomized male partners including 5, 10, or 15 intromissions. For the final test, females received 10 or 15 intromissions from male partners, were perfused one hour later, and brains and spinal cords were examined for Fos expression and LSt lesions. SSP-SAP treatment resulted in severe reduction of LSt cells, but did not affect cyclicity or expression of sexual behavior, suggesting that LSt cells are not involved in regulation of these functions. In contrast, LSt lesions significantly reduced mating-induced Fos expression in the SPFp, supporting the involvement of LSt cells in relay of VCS-related sensory information to the SPFp. However, LSt lesions did not prevent mating-induced pseudopregancy and only partly blocked mating-induced neural activation in SPFp, indicating the possible involvement of alternate pathways. Alternatively, the few remaining LSt cells in lesioned females are sufficient for induction of Fos in SPFp and pseudopregnancy.

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

Xu, WZhu JPQ, Angulo JA (2005) Ablation of NK-1 receptor-expressing interneurons prevents methamphetamine-induced apoptosis but not dopamine terminal toxicity in the striatum of mice. Neuroscience 2005 Abstracts 337.9. Society for Neuroscience, Washington, DC.

Summary: Pharmacological evidence from our laboratory demonstrates that the neurokinin-1 (NK-1) receptor mediates methamphetamine (METH)-induced toxicity of the dopamine terminals and the apoptosis of some striatal neurons. We have shown that systemic administration of the NK-1 receptor antagonist, WIN 51,708, prior to METH exposure, can protect the striatum from METH-induced damage at pre- and post-synaptic sites. To further assess the role of the NK-1 receptor on METH-induced striatal neural damage, NK-1 receptor-expressing interneurons were selectively ablated by means of intrastriatal injections of [Sar9,Met(O2)11]substance P conjugated to the ribosomal-inactivating cytotoxin saporin (SSP-SAP). TUNEL-labeling showed that ablation of striatal neurons that express NK-1 receptors provided protection against METH-induced apoptosis of some striatal neurons. However, ablation of NK-1 receptor-expressing interneurons did not provide protection against METH-induced depletion of tyrosine hydroxylase, a reliable marker of the dopamine terminals of the strtiatum. These results suggest that METH-induced apoptosis and dopamine terminal toxicity occur via distinct mechanisms in the mouse striatum.

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

Gerashchenko D, Murillo-Rodriguez E, Blanco-Centurion C, Lin L, Nishino S, Mignot E, Shiromani PJ (2005) Adenosine levels do not increase with 6 h waking in rats with lesions of the lateral hypothalamus. Neuroscience 2005 Abstracts 63.9. Society for Neuroscience, Washington, DC.

Summary: The hypocretin neurons in the lateral hypothalamus (LH) have been implicated in wakefulness, but it is not clear which projection is responsible for the arousal. One possibility is that the LH neurons induce wakefulness by driving the basal forebrain (BF) wake-active neurons (Gerashchenko and Shiromani, Cellular & Molec Neurosci, 29: 41, 2004). Here we measure adenosine (AD) levels in the BF as a marker of arousal and test the LH-BF circuit in Sprague-Dawley rats with lesions of the LH induced by hypocretin-2-saporin. 64 days after lesions the rats were kept awake (gentle handling) for six hours (ZT 3-9) and microdialysis samples (5ul) were collected hourly for 9 hours (24h after probe stabilization). AD levels were assessed using HPLC. Hypocretin-saporin ablated 95% of the hypocretin neurons and reduced CSF hypocretin levels (-75% versus control). AD levels increased with 6h waking in saline control rats (n=9), consistent with previous studies in cats (Strecker et al., Behav Brain Res 115: 183, 2000) and rats (Murillo-Rodriguez et al., Neuroscience 123: 361, 2004). However, in rats with LH lesions (n=5) such an increase with waking did not occur. Sleep drive was measured by conducting a rodent version of a multiple sleep latency test (MSLT). In this test, conducted over 10h (from ZT2-ZT12) the rats were kept awake for 20min and then allowed 20min to sleep. The lesioned rats had more sleep during the 20min sleep periods indicating a higher sleep drive. These results suggest that in narcolepsy when the HCRT LH neurons die, there is a loss of stimulation of the wake-active BF neurons and the decline in this pathway may be the cause of the increased sleep attacks. Supported by VA Medical Research and NIH

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