ABSTRACT
Phencyclidine (PCP) has been described to exacerbate psychotic symptoms in patients suffering from schizophrenia. In rats, PCP, dose-dependently, induces hyperactivity, stereotyped behaviour and social isolation, postulated to represent the positive (hyperactivity, stereotypy) and negative (social isolation) symptoms of schizophrenia. Based on previous studies, ibotenic acid lesions in the amygdala on day 7 of life have been proposed as an animal model of psychiatric neurodevelopmental disorders like schizophrenia. The purpose of the present study was to determine whether the responsiveness to PCP on locomotor activity in animals lesioned in the amygdala on day 7 of life is different from the response to this drug in sham-operated animals. The effect of graded doses of PCP on behaviour was assessed in a small open field. Animals lesioned in the amygdala on day 7 of life appeared to be hyperresponsive to PCP compared to sham-operated animals. The hyperresponsiveness to PCP in rats lesioned in the amygdala on day 7 of life further contributes to the validation of this putative animal model of schizophrenia.
Subject(s)
Amygdala/injuries , Drug Hypersensitivity/etiology , Excitatory Amino Acid Antagonists/adverse effects , Phencyclidine/adverse effects , Schizophrenia/physiopathology , Animals , Animals, Newborn , Behavior, Animal/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Early Ambulation/veterinary , Exploratory Behavior , Habituation, Psychophysiologic/drug effects , Hyperkinesis , Male , Motor Activity , Rats , Rats, Wistar , Schizophrenia/chemically induced , Stereotyped BehaviorABSTRACT
A rat model of neurodevelopmental psychopathological disorders, designed to determine neurodevelopmental deficits following damage to the brain early in life, was used to investigate behavioural changes in adaptation and habituation to an open field and responses to different kinds of stressful events. Animals with bilateral ibotenic acid lesions in the amygdala or ventral hippocampus on day 7 or 21 of life were compared to sham-operated animals. According to the model it was assumed that behavioural changes in animals lesioned on day 7, but not in animals lesioned on day 21 of life, were caused by maldevelopment of one or more structures connected to the damaged area. Animals lesioned in the amygdala or ventral hippocampus on day 7, but not animals lesioned in these structures on day 21 of life, displayed decreased (within-session) adaptation and (between-session) habituation to the open field and a decrease in immobility in the forced swim test, whereas only animals lesioned in the amygdala displayed enhanced general activity. These results were indicative of neurodevelopmental deficits. No changes in stress-induced hyperthermia were found, while animals lesioned in the amygdala both on day 7 or 21 of life exhibited decreased conditioned ultrasonic vocalizations. These latter results suggest that the amygdala is implicated in the conditioned stress-induced response. The contribution of the present findings to the animal model of neurodevelopmental disorders like schizophrenia and possible brain structures and neurotransmitter systems involved in the neurodevelopmental deficits are discussed.
