4 research outputs found
Amygdaloid Kindling and the GABA System
The effect of increased brain GABA levels on fully kindled amygdala seizures was investigated in Long-Evans rats. The newly synthesized GABA-transaminase inhibitor, -Î-acetylenic GABA (GAG) administered on four consecutive days (100 mg/kg, followed by 50 mg/kg, i.p.) was found to either significantly reduce, or eliminate entirely, the behavioral seizures normally produced by amygdala stimulation. The effect is seen after the first injection of GAG although its magnitude was greater on subsequent days. Behavioral seizures reappeared 2 to 3 days after termination of GAG treatment. The duration of electrographic seizures (self-sustained amygdala after-discharge) was either unchanged or greater on the first day of GAG treatment, but was briefer on subsequent days. The duration of afterdischarges returned to normal levels 1 to 2 days earlier than the behavioral seizures after the termination of GAG. Picrotoxin (1.5-2 mg/kg, i.p.) did not antagonize either electrographic or behavioral effects of inhibition produced with GAG. Electrical stimulation of amygdala delivered during the initial sedation stage induced by picrotoxin resulted in further regression of kindled seizures in the majority of animals. Although in doses employed, GAG alleviates amygdaloid-kindled seizures its use requires caution in view of its ability to reduce arousal level. RĂSUMĂ L'effet de l'ĂlĂvation des taux cĂrĂbraux de GABA sur les crises amygdaliennes par effet d'embrasement complet a ĂtĂĂtudiĂ chez des rats Long-Evans. l'injection pendant 4 jours consĂcutifs de 100 mg/kg suivis de 50 mg/kg i.p. d'un inhibiteur de la GABA. Transaminase nouvellement synthĂtisĂ (Î-acetylenic GABA ou GAG) a significativement rĂduit ou mĂme supprimĂ les crises normalement provoquĂes par la stimulation amygdalienne. l'effet est observĂ aprĂs la premiere injection de GAG, mais son importance s'accroit les jours suivants. Les crises rĂapparaissent 2 ou 3 jours aprĂs la fin du traitement au GAG. Du point de vue Ălectrographique, la durĂe de la postdĂcharge amygdalienne autoentretenue est inchingĂe ou accrue le premier jour du traitement, mais elle diminue les jours suivants pour retourner Ă la normale un ou deux jours avant que les crises ne rĂapparaissent aprĂs la fin de ('administration du GAG. l'injection de picrotoxine (1.5-2 mg/kg i.p.) ne s'oppose pas aux effets inhibiteurs du GAG sur les crises ou leur accompagnement EEG. La stimulation Ălectrique de l'amygdala pendant l'Ătape sĂdative initiate induite par la picrotoxine provoque une rĂgression supplĂmentaire des crises d'embrasement chez la majoritĂ des animaux. Bien que, aux doses utilisĂes, le GAG attĂnue les crises amyg-daliennes d'embrasement, son utilisation nĂcessite des prĂcautions compte tenu de sa tendance Ă rĂduire le niveau d'Ăveil. RESUMEN En ratas Long-Evans se ha investigado el efecto del aumento de los niveles cerebrales de GABA, sobre los ataques originados en la amĂgdala totalmente condicionada, (Kindling). El recientemente sintetizado in-hibidor de la GABA transaminasa, Î-acetilĂnico GABA (GAG), redujo significativamente o eliminĂ totalmente las crisis de comportamiento que habitualmente se producen con la estimulaciĂn de la amĂgdala. El efecto se observa despuĂs de la primera in-yecciĂn de GAG pero su magnitud aumentĂ en dias subsiguientes. Las crisis de comportamiento reaparecieron a los 2â3 dĂas de la interrupciĂn del tratamiento con GAG. La duraciĂn de los ataques electrogrĂficos (perservaciĂn de la post-descarga de la amigdala) no se modificĂ, o incluso aumentĂ, en el primer dia de la administraciĂn de GAG pero se redujo en los dias siguientes. La duraciĂn de las post-descargas volviĂ a sus niveles normales 1 o 2 dias antes que la reapariciĂn de las crisis de comportamiento una vez terminado el tratamiento con GAG. La picrotoxina (1.5-2 mg/kg, i.p.) no antagonizĂ los efectos inhibitorios producidos por el GAG sobre el electroencefalograma o las crisis de comportamiento. La estimulaciĂn elĂctrica sobre la amĂgdala, aplicada durante la fase de sedaciĂn inicial inducida por la picrotoxina, condujo a una regresiĂn aĂn mĂs intensa de las crisis condicionadas, en la mayorĂa de los animales. A pesar de que, con las dosis utilizadas, el GAG alivia las crisis de la amĂgdala previamente condicionada, se requiere gran precauciĂn en su utilizaciĂn en vista de su propiedad de reducir el nivel del despertar. ZUSAMMENFASSUNG Die Wirkung erhĂhter GABA-Spiegel des Gehirns auf AmygdalonkrĂmpfe nach Kindling wurden bei Long-Evans-Ratten untersucht. Der neuerdings synthetisierte GABA-TYansaminasen-Inhibitor, Gamma-Acetylen-GABA (GAG) wurde an 4 aufeinander-folgenden Tagen in einer Dosis von 100 mg/kg und anschlieliend 50 mg/kg i.p. verabfolgt. Er reduzierte entweder signifikant oder eliminierte vĂllig die anfalls-weisen VerhaltensĂnderungen, die normalerweise durch Stimulation des Amygdalon produziert wurden. Die Wirkung ist nach der Erstinjektion des GAG zu beobachten, obgleich ihr AusmaĂ an folgenden Tagen grĂĂer war. Die VerhaltensanfĂlle kamen 2 bis 3 Tagen nach Beendigung der GAG-Behandlung wieder. Die Dauer der elektrographischen AnfĂlle (sich selbst un-terhaltende Amydalonnachentladungen) blieben entweder gleich oder sie wurden grĂĂer am 1. Tag der GAG-Behandlung, wurden aber kĂrzer an folgenden Tagen. Die Dauer der Nachentladungen nor-malisierte sich 1 bis 2 Tage frĂher als die VerhaltensanfĂlle nach Beendigung des GAG verschwanden. Picrotoxin (1.5 bis 2 mg/kg i.p.) wirken nicht als Antagonist gegenĂber der durch GAG produzierten Hemmung der elektrographischen-oder Verhalten-seffekte. Die elektrische Stimulierung des Amygdalon wĂhrend der initialen Sedierung nach Picrotoxin ver-ursachte bei der Mehrzahl der Tiere einen weiteren RĂckgang der durch Kindling entstandenen AnfĂlle. Obgleich das GAG in den verwandten Dosen, die durch Kindling des Amygdalon erzeugten KrĂmpfe leichter ablaufen lUĂt, erfordert seine Anwendung Vorsicht hinsichtlich seiner FĂhigkeit, das Erreg-barkeitsniveau zu senken.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66112/1/j.1528-1157.1980.tb04058.x.pd
Carnosine (ÎČ-alanyl-L-histidine) increases the efficacy of learning under conditions of oxidative stress related to the development of conditioned response with negative reinforcement
Impaired associative learning in schizophrenia: behavioral and computational studies
Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and frontoâhippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia