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      Evaluación de la Nicotina como Estímulo Aversivo Translated title: Nicotine Assessment as an Aversive Stimulus

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          Abstract

          La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales.

          Translated abstract

          Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to evaluated the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose, however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.

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          Most cited references40

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          The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls.

          Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n=28) and healthy controls (n=32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebo-controlled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.
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            Conditioned taste aversion as a learning and memory paradigm.

            Conditioned taste aversion (CTA) is a well established learning and memory paradigm in rats and mice that is considered to be a special form of classical conditioning. Rodents--as well as many other species including man--learn to associate a novel taste (CS) with nausea (US), and as a consequence avoid drinking fluid with this specific taste. In contrast to other types of classical conditioning, even CS-US intervals lasting several hours lead to an aversion to the gustatory CS. With increasing CS-US delay duration, however, the aversion against the CS gradually decreases. Mice differ from rats in their reaction to the CS as well as the US. They tolerate a much higher concentration of saccharin and they do not show any clear signs of nausea when injected with the US. Advantages of this task are its relative independence of motor behavior, well described pathways for the CS and partly the US, and the wealth of available anatomical and pharmacological data implying several brain structures (e.g. parabrachial nucleus, amygdala, insular cortex), neurotransmitters and their receptors (e.g. cholinergic system, NMDA-receptors), and cellular processes (e.g. expression of immediate early genes, Ras-MAP kinase signaling pathway, CREB phosphorilation, protein tyrosine phosphorilation, protein synthesis) in CTA. The CTA paradigm has also been successfully used to phenotype mouse mutants.
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              Nicotinic acetylcholine receptors in the mesolimbic pathway: primary role of ventral tegmental area alpha6beta2* receptors in mediating systemic nicotine effects on dopamine release, locomotion, and reinforcement.

              alpha6* nicotinic acetylcholine receptors (nAChRs) are highly and selectively expressed by mesostriatal dopamine (DA) neurons. These neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Yet the functional role of alpha6* nAChRs in midbrain DA neurons is mostly unknown. The aim of this study was to determine the composition and in vivo functional role of alpha6* nAChR in mesolimbic DA neurons of male rats. Immunoprecipitation and immunopurification techniques coupled with cell-specific lesions showed that the composition of alpha6* nAChR in the mesostriatal system is heterogeneous, with (non-alpha4)alpha6beta2* being predominant in the mesolimbic pathway and alpha4alpha6beta2* in the nigrostriatal pathway. We verified whether alpha6* receptors mediate the systemic effects of nicotine on the mesolimbic DA pathway by perfusing the selective antagonists alpha-conotoxin MII (CntxMII) (alpha3/alpha6beta2* selective) or alpha-conotoxin PIA (CntxPIA) (alpha6beta2* selective) into ventral tegmental area (VTA). The intra-VTA perfusion of CntxMII or CntxPIA markedly decreased systemic nicotine-elicited DA release in the nucleus accumbens and habituated locomotion; the intra-VTA perfusion of CntxMII also decreased the rate of nicotine infusion in the maintenance phase of nicotine, but not of food, self-administration. Overall, the results of these experiments show that the alpha6beta2* nAChRs expressed in the VTA are necessary for the effects of systemic nicotine on DA neuron activity and DA-dependent behaviors such as locomotion and reinforcement, and suggest that alpha6beta2*-selective compounds capable of crossing the blood-brain barrier may affect the addictive properties of nicotine and therefore be useful in the treatment of tobacco dependence.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                aip
                Acta de investigación psicológica
                Acta de investigación psicol
                Universidad Nacional Autónoma de México, Facultad de Psicología (México )
                2007-4719
                2015
                : 5
                : 1
                : 1916-1925
                Affiliations
                [1 ] Universidad Nacional Autónoma de México Mexico
                [2 ] Universidad Nacional Autónoma de México Mexico
                Article
                S2007-48322015000101916
                2b251e34-12ae-4f4c-8bb2-5c3eb9913efd

                http://creativecommons.org/licenses/by/4.0/

                History
                Categories
                Nuclear Science & Technology
                Psychology
                Psychology, Applied
                Psychology, Developmental
                Psychology, Educational
                Psychology, Experimental

                Nuclear chemistry,Clinical Psychology & Psychiatry
                CTA,Nicotine,Saccharin,CS,US,CAS,Nicotina,Sacarina,Neofobia,EC,EI
                Nuclear chemistry, Clinical Psychology & Psychiatry
                CTA, Nicotine, Saccharin, CS, US, CAS, Nicotina, Sacarina, Neofobia, EC, EI

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