Receptors knock-out mice

IL-ip is a well documented sleep factor (reviewed by Obal Krueger, 2003). Its administration increases sleep, its blockade decreases sleep and sleep rebound, and its transcription increases during waking. IL-1 receptor knock-out mice sleep less. Local application of IL-1 p in POA also stimulates NREM sleep. We examined the effects of local administration of IL-1 p and an antagonist through microdialytic application adjacent to lateral POA neurons (Alam et at, 2004). Neuronal activity is recorded within 0.5-1.0 mm of a microdialysis membrane in unrestrained rats. IL-ip potently inhibited the activity of 79% of wake-active neurons. The inhibitory response to IL-ip of wake-active neurons could be blocked by pre-treatment with IL-lra, an IL-ip antagonist. IL-ip application also excited some sleep-active neurons, but this response was inconsistent. 

Clemens S., Hochman S. (2004). Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice. J. Neurosci 24, 11337-45. 

Berrendero, R., Kieffer, B., Maldonado, R. Attenuation of nicotine-induced antinociception, rewarding effects and dependence in mu-opioid receptor knock out mice. J. Neurosci. 22 10935, 2002. 

Wess, J. Muscarinic receptor knock out mice novel phenotypes and clinical implications. Ann. Rev. Pharmacol. Toxicol. 44,423-500, 2004. 

Zhang, W., Basile, A. S., Gomeza, J., Volpicelli, L. A., Levey, A. I. and Wess, J. Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice. /. Neurosci. 22 1709-17, 2002. 

Froger N, Gardier AM, Moratalla R, Alberti I, Lena I, Boni C, De Felipe C, Rupniak NM, Hunt SP, Jacquot C, Hamon M, Lanfumey L (2001) 5-hydroxytryptamine (5-HT)lA autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization. J Neurosci 21 8188-8197 Gardier AM, Bourin M (2001) Appropriate use of knockout mice as models of depression or models of testing the efficacy of antidepressants. Psychopharmacology (Berl) 153 393-394... 

EP1 receptor knock-out mice show reduced pain sensitivity, suggesting an important role for this receptor subtype in pain perception (Stock et al., 2001). Furthermore these mice show a significant reduction in systolic blood pressure and an increased renin angiotensin activity, suggesting a role also in cardiovascular homeostasis. 

Studies with CBi receptor knock-out mice suggest the existence of an as yet unknown neuronal cannabinoid receptor -potentially a new target for pain research... 

Further experimental evidence for the involvement of SP in pain perception came from knock-out animals. Mice, in which the preprotachykinin A gene was disrupted, showed significantly reduced responses in tests that involved more intense noxious stimuli (Cao et al., 1998). De Felipe et al. (1998) disrupted the N receptor, and found the characteristic amplification ( wind up ) and intensity coding of nociceptive reflexes to be absent. NK receptor knockout mice show no changes in acute nociception tests. In contrast, SP and NKi receptor knock-out mice show reduction in responses to inflammatory stimuli. Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in NKi receptor knock-out mice, when inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve (Mansikka et al., 2000). 

Zhang W, Yamada M, Gomeza J, Basile AS, Wess J (2002b) Multiple muscarinic acetylcholine receptor subtypes modulate striatal dopamine release, as studied with M1-M5 muscarinic receptor knock-out mice. J Neurosci 22 6347-52... 

Sarhan H, Grimaldi B, Hen R, Fillion G (2000) 5-HTib receptors modulate release of [3H] dopamine from rat striatal synaptosomes further evidence using 5-HT moduline, polyclonal 5-HT is receptor antibodies and 5-HT ib receptor knock-out mice. Naunyn Schmiedebergs Arch Pharmacol 361 12-18... 

Compan V, Zhou M, Grailhe R, et al. Attenuated response to stress and novelty and hypersensitivity to seizures in 5-HT4 receptor knock-out mice. J Neurosci 2004 24 412-419. 

Malleret G, Hen R, Guillou JL, Segu L, Buhot MC. 5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze. J Neurosci 1999 19(14) 6157-6168. 

Malagie I, David DJ, Jolliet P, Hen R, Bourin M, Gardier AM. Improved efficacy of fluoxetine in increasing hippocampal 5-hydroxytryptamine outflow in 5-HT(lB) receptor knock-out mice. Eur J Phannacol 2002 443 99-104. 

In the lateral part of the SNc, VTA and A8 retrorubral field, all the TH-positive cells displayed D3 receptor immunoreactivity in contrast, some D3-positive cells were TH-immunonegative (Diaz et al., 2000). These results support the initial finding that D3 receptors act as autoreceptors (Sokoloff et al., 1990), as well as the report, based on the study of D3 receptor mRNA, in which the SNc lateral part was shown to express D3 receptor transcript (Bouthenet et al., 1991). Electrophysiological studies, however, showed that autoreceptor functions are maintained in D3 receptor-knock out mice, indicating that the D2 receptor is the major autoreceptor (Koeltzow et al., 1998). 

Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA (1999) Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. J Neurosci 79 9550-9556. 

Elmer GI, Pieper JO, Rubinstein M, Low MJ, Grandy DK, Wise RA (2002) Failure of intravenous morphine to serve as an effective instrumental reinforcer in dopamine D2 receptor knock-out mice. J Neurosci 22 RC224. 

Accili, t). (1997). Insulin receptor knock-out mice. Trends Endocrinol. fAetab- 8, 101-104. 

Korach, K.S. Estrogen receptor knock-out mice molecular and endocrine phenotypes. J. Soc. Gynecol. Invest. 1 S16-S17, 2000. 

Reibaud M, Obinu MC, Ledent C, Parmentier M, Bohme GA, Imperato A (1999) Enhancement of memory in cannabinoid CBi receptor knock-out mice. Eur J Pharmacol 379 R1-R2... 

Parmentier-Batteur S, Jin K, Mao XO, Xie L, Greenberg DA (2002) Increased severity of stroke in CBI cannabinoid receptor knock-out mice. J Neurosci 22 9771-9775... 

Pacher P, Batkai S, Kunos G (2004) Haemodynamic profile and responsiveness to anandamide of TRPVl receptor knock-out mice. J Physiol (Lond) 558 647-657... 

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