en Movement disorders پژوهشي Research Article <span style="font-size:12pt"><span style="line-height:200%"><span new="" roman="" style="font-family:" times=""><span style="font-family:" times-roman="">A lower level of brain substance P (SP) is detected in Parkinson&rsquo;s disease; apparently, central SP-ergic deficiency takes place in Parkinsonian patients. The pathogenic relevance of this abnormality is unknown.&nbsp; Another understudied area is the influence of early-life adversities on Parkinsonism.&nbsp; Here, we hypothesized that i) simulation of central SP hypoactivity by intracerebral injections of NK1 receptor antagonist can initiate catalepsy, a model of Parkinsonian bradykinesia and rigidity, ii) early-life maternal separation (MS) can influence the SP-dependent catalepsy; and iii) the above catalepsy can be regulated by the blockade of CRF₁ receptors. The study was performed on Wistar rats. MS of pups was carried out at postnatal days 2-14 for 3 h per day. In adulthood (16-17 weeks of age), one hundred ninety-two males with MS history (weight 280-310 g) were examined behaviorally; catalepsy was assessed by a bar test. In undisturbed animals, i.c.v. administration of NK1 receptor antagonist L-733,060 at 10.0 ng produced clear catalepsy, the drug at the dose of 1.0 ng was ineffective.&nbsp; MS&nbsp; <i>per se</i> failed to exert catalepsy, however, in the MS-exposed rats, L-733,060 at 1.0 ng produced strong cataleptic response.&nbsp; Thus, the blocker of NK1 receptors and MS supra-additively initiated&nbsp; the development of catalepsy. This catalepsy was significantly reversed by NBI 35 965, an antagonist of CRF₁ receptors.&nbsp;&nbsp; Our findings show, for the first time, that the blockade of central NK1 receptors can induce catalepsy; this cataleptic response is synergistically potentiated by MS and is mediated by CRF₁ receptors. These data suggests that the combination of central NK1 receptor hypofunctioning&nbsp;&nbsp; and&nbsp;&nbsp; neonatal stress may dysregulate&nbsp; the extrapyramidal system. Apparently, the central processes mediated by NK1 and CRF₁ receptors might&nbsp; be potential therapeutic targets for Parkinsonism.</span></span></span></span><br> <br> <br> &nbsp; NK1 receptors, CRF1 receptors, substance P, maternal separation, catalepsy 57 64 http://ajnpp.umsha.ac.ir/browse.php?a_code=A-10-948-2&slc_lang=en&sid=1 Ilya Ionov newrology@yandex.ru 10031947532846007613 10031947532846007613 Yes Head, Department of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, 109029, Russia Maria D. Krasilova Newrology-mdk@yandex.ru 10031947532846007614 10031947532846007614 No Senior Researcher, Department of Neurology, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, 109029, Russia Margarita O. Lyubimova marlyub.n-res@yandex.ru 10031947532846007615 10031947532846007615 No Researcher, Department of Neurology, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, 109029, Russia Nina Morozova nimor.ir@mail.ru 10031947532846007616 10031947532846007616 No Researcher, Department of Neurology, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, 109029, Russia Lyudmila Maltseva limalts-prk@yandex.ru 10031947532846007617 10031947532846007617 No Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, 109029, Russia Piotr Komikarov komikarov@mail.ru 10031947532846007618 10031947532846007618 No Timpharm LTD, Moscow, 117513, Russia