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Oleic Acid Produces Motor Incoordination and Hypoactivity in Infant Wistar Rats Through GABAA Receptors

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Oleic Acid Produces Motor Incoordination and Hypoactivity in Infant Wistar Rats Through GABAA Receptors American Journal of Psychiatry and Neuroscience 2016; 4(2): 18-25 http://www.sciencepublishinggroup.com/j/Ajpn doi: 10.11648/j.Ajpn.20160402.11 ISSN: 2330-4243 (Print); ISSN: 2330-426X (Online) Oleic Acid Produces Motor Incoordination and Hypoactivity in Infant Wistar Rats Through GABAA Receptors Gabriel Guillén-Ruiz1, Blandina Bernal-Morales1, Carlos M. Contreras1, 2, *, Jonathan Cueto-Escobedo1, Juan Francisco Rodríguez-Landa1 1NeurophArmAcology Section, Institute of Neuroethology, University of VerAcruz, XAlApA, VerAcruz, México 2PeripherAl Unit, BiomedicAl ReseArch Institute, NAtionAl Autonomous University of México, XAlapA, VerAcruz, México Email address: [email protected] (G. Guillén-Ruiz), [email protected] (B. BernAl-MorAles), [email protected] (C. M. ContrerAs), [email protected] (J. Cueto-Escobedo), [email protected] (J. F. Rodríguez-LAndA) *Corresponding Author To cite this article: Gabriel Guillén-Ruiz, BlAndinA BernAl-MorAles, CArlos M. ContrerAs, JonAthAn Cueto-Escobedo, JuAn FrAncisco Rodríguez-LAndA. Oleic Acid Produces Motor IncoordinAtion And HypoActivity in InfAnt WistAr Rats Through GABAA Receptors. American Journal of Psychiatry and Neuroscience. Vol. 4, No. 2, 2016 pp. 18-25. doi: 10.11648/j.ajpn.20160402.11 Received: MArch 8, 2016; Accepted: MArch 18, 2016; Published: MArch 31, 2016 Abstract: A mixture of eight fAtty Acids (linoleic, oleic, pAlmitic, steAric, myristic, elAidic, lAuric, And pAlmitoleic Acids) At similAr concentrAtions thAt hAve been identified in humAn Amniotic fluid exerts anxiolytic-like effects similAr to diAzepAm in adult Wistar rats through actions at γ-aminobutyric Acid-A (GABAA) receptors, but unknown is whether Any of these fAtty Acids exerts a predominant action over the others in infAnt rAts. Of these fAtty Acids, some Actions of oleic acid hAve already been identified, And it is one of the most AbundAnt in Amniotic fluid. Therefore, the Aim of this study wAs to explore the effect of oleic acid on anxiety-like behAvior and motoric activity in infAnt rAts. To explore sedAtive Actions, 28-dAy-old WistAr rAts received 80-320 µg oleic Acid or A sedative dose of diAzepAm (5 mg/kg). In a dose-response study, other groups of rAts were injected with 10-80 µg oleic Acid or 1 mg/kg diAzepAm. In An interaction study, rats thAt received oleic Acid were pretreAted with the GABAA receptor AntAgonists picrotoxin or flumAzenil to explore the participation of this receptor in the effects of oleic acid on behavior in the elevAted plus mAze, rotarod test, And open field test. Oleic Acid produced sedative effects but did not exert Any Anxiolytic-like actions. Hypoactivity And motor incoordination that were induced by oleic Acid were blocked by flumAzenil And picrotoxin. In conclusion, oleic acid reduced locomotor activity And motor incoordination through Actions At the GABAA receptor. Keywords: HypoActivity, Motor IncoordinAtion, FAtty Acids, Oleic Acid, Anxiety 1. Introduction indicAting the pArticipAtion of γ-aminobutyric Acid-A (GABAA) receptors [7]. Amniotic fluid And colostrum Are Able to promote useful GABAA receptors cAn be blocked by antAgonists, such as emotionAl responses in offspring (e.g., orientAtion and picrotoxin And flumAzenil. These AntAgonists block the bonding in lAmbs through individuAl odors to ensure survivAl anxiolytic, sedative, ataxic, and motor incoordination effects [1] or the odor of rat dAms to leArn filiAl huddling preferences of benzodiAzepines And bArbiturAtes [8]. FlumAzenil is a [2]). HumAn newborns who Are exposed to scents from their selective AntAgonist of the benzodiAzepine Allosteric binding own Amniotic fluid exhibit A reduction of crying when the site, whereAs picrotoxin is A noncompetitive AntAgonist of mother is Absent [3]. AppArently, these effects Are mediAted GABAA receptors thAt blocks chloride ion chAnnels [8]. by fAtty Acids thAt Are contAined in humAn mAternAl fluids, Therefore, these AntAgonists constitute effective tools in the which Are Also Able to produce Appetitive reActions in humAn phArmAcologicAl screening of drugs thAt interAct with newborns [4] And Anxiolytic-like Actions that Are compArAble GABAA receptors [9]. to diazepAm in mAle And femAle Adult Wistar rAts [5, 6]. Oleic Acid increAses the Affinity of flunitrAzepAm and These effects Are blocked by pretreAtment with picrotoxin, muscimol, suggesting Actions At the benzodiAzepine site of 19 GAbriel Guillén-Ruiz et al.: Oleic Acid Produces Motor IncoordinAtion And Hypoactivity in InfAnt WistAr Rats Through GABAA Receptors the GABAA receptor [10, 11], and modulAtes the opening of 2.2. Experimental Design chloride channels [12]. We previously demonstrated thAt oleic Acid is the second most Abundant fAtty Acid in humAn 2.2.1. Sedative Study amniotic fluid, colostrum, and milk [4]. Oleic acid is A Oleic Acid wAs studied to evAluAte its Ability to cause monounsAturAted fAtty Acid (C18:1n9) thAt is widely sedAtion. SubcutAneous doses of 80 or 320 µg were chosen distributed in nAture And the most Abundant in such vegetAble based on the oleic Acid content in 1 ml of Amniotic fluid (80 products As AvocAdos And olives [13, 14]. This mAy explain µg/rat) as the initial point. Two groups of PND28 rats (n = 6 the importance of consumption of the MediterrAneAn diet per group) were injected with 80 or 320 µg oleic Acid And (i.e., fruits, vegetAbles, legumes, And nuts), in which wheAt compared to a group that was injected with 5 mg/kg and olive oil Are the principAl fats [15]. The MediterrAneAn diAzepAm (n = 6) As a sedAtive reference drug and to a vehicle diet AppArently produces beneficiAl effects thAt mAintAin group (n = 6). Two experimentAl observers evAluAted heAlth compAred with other diets with A low content of these behAvior every 5 min for A totAl of 120 min After the fatty Acids [16]. EpidemiologicAl And preclinicAl studies hAve injections. The scoring system wAs on A 0-4 scAle, where 0 = suggested some supposedly protective cArdiovAsculAr [17], alert and completely responsive, 1 = alert but less active And antiinflAmmatory [18], antioxidant [16, 19], and antitumor “wobbly,” 2 = Awake but drowsy with periods of inactivity or [20] effects of oleic Acid, but the results hAve not been mild sedAtion, 3 = inActive but reAdily ArousAble or conclusive. moderAtely sedAted, And 4 = unresponsive, unconscious, or Most preclinicAl studies hAve focused on identifying deeply sedated [25]. Scores were AverAged Across treatment anxiolytic and motor effects by employing adult subjects, groups per time point. but Anxiety-relAted behAviors And phArmAcologicAl 2.2.2. Oleic Acid Dose-Response Study sensitivity cAn be Age-dependent [21]. Anxiety cAn be To explore Any Anxiolytic-like And motor effects of oleic detected At eArly Ages [21, 22], but substAnces with acid, the rats were assigned to five experimental groups: (i) 10 anxiolytic actions in infant rats have been scarcely explored. µg (n = 12), (ii) 20 µg (n = 15), (iii) 40 µg (n = 14), (iv) 60 µg Therefore, the present study evAluAted the effects of oleic (n = 10), and (v) 80 µg (n = 10), which is equivAlent to the acid on anxiety-like behavior and locomotor activity in amniotic fluid concentrAtion [5]. The dAtA were compared infAnt rAts. We Also explored the pArticipAtion of GABAA with A vehicle group (n = 10) and 1 mg/kg diazepAm group (n receptors in these Actions by using the benzodiAzepine = 12) as a reference anxiolytic drug. steAric receptor blocker flumAzenil And GABAA receptor chloride channel blocker picrotoxin in infant (postnatAl dAy 2.2.3. Interaction Between Oleic Acid and GABAA Receptor [PND] 28) WistAr rats. Antagonists Another four experimentAl groups were included to identify 2. Materials and Methods the mechAnism of Action of oleic Acid. The first group received flumAzenil (5 mg/kg, n = 9) 30 min before oleic acid All of the procedures followed the principles of AnimAl cAre administration (80 µg). The second group received picrotoxin based on the Guide for the Care and Use of Laboratory Animals (1 mg/kg, n = 10) 30 min before oleic acid administrAtion. [23] And MexicAn OfficiAl Norm for CAre And Use of Lab These results were compAred with An oleic Acid group (80 µg, AnimAls [24]. The experimentAl protocol received AuthorizAtion n = 10) and a vehicle group (n = 10). All of the injections were from the BiomedicAl ReseArch Institute EthicAl Committee, administered subcutAneously in a volume of 1 ml, 1 h before NationAl Autonomous University of Mexico (UNAM). the behAviorAl tests, with the exception of the Antagonists in the interAction study thAt were dissolved in isotonic sAline 2.1. Animals solution And Administered intrAperitoneAlly in A volume of 0.5 The experiments included offspring from WistAr rAts, ml 30 min before the oleic Acid injection. provided by the BiomedicAl ReseArch Institute, UNAM. 2.3. Drugs During gestAtion And After delivery, eAch dAm And its litter of 8-10 pups remAined in Acrylic boxes (44 cm × 33 cm bAse, 20 Oleic Acid wAs prepAred According to previous studies at A cm height) under A 12 h/12 h light/dArk cycle (lights on At 7:00 concentration similar to that found in humAn Amniotic fluid [5], AM) with free Access to food (TeklAd LAb AnimAl Diets, which produces hypoActivity in Adult rAts [26]. The HarlAn, IndiAnApolis, IN, USA) And purified wAter. The nest preparAtion consisted of oleic Acid (8 mg) dissolved in 100 ml remAined undisturbed, And the dAms And pups were minimAlly of vehicle (96% propylene glycol And 4% ethAnol) At a handled while changing the bedding mAteriAl (every 48 h). temperAture < 40ºC. For the sedAtive study, 32 mg oleic Acid The offspring were weAned on PND21 And AllocAted to six to was dissolved in 100 ml of vehicle. Oleic Acid, flumazenil, And eight animals per cage (44 cm × 33 cm bAse, 20 cm height). On picrotoxin were AnAlyticAl grAde And purchAsed from PND28, the offspring were rAndomly Assigned to the SigmA-Aldrich (St. Louis, MO, USA). Propylene glycol And experimental groups and immediately underwent behAviorAl ethanol were obtained from J.T.
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