Реферат
Ethanol exerts its behavioral effects largely by interacting with receptors to brain neurotransmitters. The molecular mechanisms involving these interactions are still not well known since an ideal model for their study is currently unavailable. In addition, responses to alcohol may vary due to factors such as genetic predisposition, ethanol concentration consumed, and stimuli such as stress, socialization, etc. The chronc consumption of alcohol, similar to that of other drugs such as benzodiazepines and barbiturates, is linked to GABAerigc neurotransmission. GABA is the predominant inhibitory neurotransmitter in the brain. In context of substance abuse, these three drugs first cause a gratifying effect, later tolerance and finally, physical and psychological dependence. If cosumption is interrupted abruptly, a withdrawal syndrome occurs. The Alcohol Withdrawal Syndrome (AWS) is state of hyperexcitability characterized by anxiety, fear, muscular rigidity and tonic-clonic seizures with epileptiform-type charactermental epilepsy models such as "Kindling" or GABA Withdrawal Syndrome (GWS) models. A possible correlation between these models and AWS will allow for a better understanding of the cellular and molecular effects that alcohol exerts on the brain
Тема - темы
Animals , Alcoholism/complications , Alcoholism/physiopathology , Anti-Anxiety Agents/pharmacology , Cerebrum/drug effects , Cerebrum/physiopathology , Epilepsy/complications , Epilepsy/physiopathology , gamma-Aminobutyric Acid/physiology , Receptors, GABA-A/physiology , Disease Models, Animal , Drug Tolerance , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , Hypnotics and Sedatives/pharmacology , Models, Neurological , Receptors, GABA-A/drug effects , Receptors, Glutamate/drug effects , Synaptic TransmissionТема - темы
Humans , Anesthetics, General/pharmacokinetics , Ion Channels , Membranes/drug effects , Calcium Channels/drug effects , gamma-Aminobutyric Acid/drug effects , Potassium Channels/drug effects , Receptors, Nicotinic , Receptors, Glutamate/drug effects , Receptors, Glycine/drug effects , Sodium Channels/drug effectsРеферат
The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation.The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular relfex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamatae microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory componente of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.
Тема - темы
Rats , Animals , Cardiovascular System/drug effects , Chemoreceptor Cells/physiology , Glutamic Acid/pharmacology , Glycine/pharmacology , Potassium Cyanide/pharmacology , Pressoreceptors/physiology , Receptors, Glutamate/drug effects , Reflex/physiology , Serotonin/pharmacology , Solitary Nucleus/physiology , Chemoreceptor Cells/drug effects , Pressoreceptors/drug effectsРеферат
Several experimental models have been used to study tolerance to ethanol. The development of tolerance to the motor incoordinating effect of a single administration of ethanol occurs within 8-24 h after the effect of the first dose has disappeared. This form of tolerance is designated rapid tolerance and seems to involve functional rather than pharmacokinetic mechanisms. Like chronic tolerance, rapid tolerance has been shown to be infiuenced by processes related to learning and memory. It is known that N-methyl-D-aspartate (NMDA) receptor systems are involved in the expression and maintenance of one form of long-term potentiation (LTP), a synaptic adaptive process which has been suggested to be the cellular basis of memory or associative memory. Considering the similarities between learning and tolerance, the effects of NMDA agonists and antagonists on tolerance to ethanol were investigated. Our studies demonstrated that NMDA antagonists that impair learning, such as dizocilpine or ketamine, inhibit tolerance, while NMDA agonists that improve learning, such as D-cycloserine, increase tolerance. Moreover, the nitric oxide synthase inhibitor L-nitroarginine blocks tolerance to the effects of ethanol. Taken together, these data confirm the involvement of the NMDA system in ethanol tolerance and emphasize the participation of leaming in this phenomenon.