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dc.contributor.authorMartínez Rivera, Arlene
dc.contributor.authorMaldonado-Vlaar, Carmen S. (Consejera)
dc.date.accessioned2015-11-21T21:25:51Z
dc.date.available2015-11-21T21:25:51Z
dc.identifier.urihttp://hdl.handle.net/123456789/2321
dc.description.abstractDrug abuse is one of the major public health concerns affecting our society and an effective treatment for this pathology has not yet been developed. Addiction is defined as a chronic relapsing brain disease characterized by the compulsive use of drugs despite its harmful consequences (National Institute of Abuse (NIDA)). Drugs such as cocaine can cause addiction resulting in neurobiological and behavioral changes. These neurobiological changes make the person more susceptible to relapse after periods of abstinence. There are three main factors that can precipitate relapse in an addict; acute exposure to the drug, stress and environmental stimuli associated with previous drug use. It has been imperative and a challenge in the field of drug abuse to understand why environmental cues previously paired with drug use can elicit relapse after periods of abstinence. The present thesis seeks to contribute to the present knowledge related to the neurobiological substrates of cues-induced drug seeking behavior. Addiction studies have identified different brain regions that are affected by drugs abuse, among them the nucleus accumbens (NAc). The NAc is localized within the ventral region of the corpus striatum (Str) and has been directly implicated in the mediation of psychostimulant-induced locomotor activity via dopamine (DA) and glutamate neurotransmission (Vezina & Kim, 1999). DA neurotransmission to the NAc is associated with reward and motivation, outputs from the NAc are associated with motor execution of goal-directed behavior (Kelley, 1999, Groenewegen, 1999), giving the NAc a dual function in the reward system. Based on its connections, the NAc have been divided in two subregions: the NAc shell and NAc core (Zahm & Brog, 1992). The shell has been implicated in the modulation of emotion while the core modulates the motor responses related to reward. A better understanding of the different genes or proteins within the NAc affected by cocaine exposure would help in identifying targets for specific pharmacotherapeutic clinical treatment. Appropriate targets may include Excitatory Amino Acid (EAA) receptors. EAA neurotransmission within the NAc helps to regulate the neural mechanisms underlying learning and memory processes that register environmental stimuli promoting drug use. EAA exert their action trough ionotropics and metabotropics receptors. There are eight metabotropic glutamate receptors (mGluRs) subtypes classified into three groups (Conn and Pin, 1997). All mGluRs groups are found in NAc subregions and have been implicated in mediating cocaine addiction, specifically mGluRs subtypes 1 and 5. Group I mGluRs are associated to the Homer proteins, a family of synaptic proteins that anchor mGluR1/5 at the excitatory synapse and are implicated in the psychomotor effects of cocaine. Moreover, the Homer protein dependent-pathway has been linked to extracellular signal-regulated kinases (ERK) 1/2 and the subsequent activation of several transcription factors that may play a role in the associative learning involved in cocaine conditioning. Even when there is extensive evidence that related mGluR5 in the modulation of different cocaine exposure paradigms, such as cocaine seeking behavior, and cocaine induced locomotion sensitization, there is not much evidence that can establish how mGluR5 within the NAc shell modulate environmental elicited cocaine locomotion conditioning. Moreover, it is not well known how development of locomotion conditioning affects mGluR5 and Homer1b/c protein expression within the NAc subregions. Thus, the present thesis further examines the role of mGluR5 within the NAc shell in the expression of environmental elicited cocaine conditioning. We were able to confirm the role of mGluR5 in cocaine conditioning paradigm. In addition, we established that mGluR5 and Homer 1b/c is not affected during acquisition neither expression of the conditioning. Furthermore, we believe that even when proteins expression of mGluR5 and Homer 1b/c is not affected their interaction is important for the downstream events that are activated and modulating the expression of the conditioning. Even when pERK1/2 was not affected in the later time of the expression of the conditioning, we assume that an early activation of ERK1/2 account for the later response of the conditioning
dc.language.isoen
dc.subjectAddiction
dc.subjectmGluR5
dc.subjectCocaine conditioning
dc.subjectNucleus acumbens
dc.subjectDrug abuse
dc.subjectbiology
dc.titleBehavioral and Intracellular Mechanisms of mGluR5 within the Nucleus Acumbens Shell During Expression of Environmental Elicited Cocaine Conditioning
dc.typePhD Dissertation


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