RESUMO
A paradigm based on conditioned suppression of ongoing motor activity, sensitive to latent inhibition (LI), was developed and tested in healthy volunteers. Subjects were trained to move disks from one peg to another with a high degree of regularity in the Tower of Toronto puzzle, a well-known cognitive skill learning task. Once this was achieved, they were submitted to a Pavlovian conditioning procedure. The conditioned stimulus (CS) was a pure tone and the unconditioned stimulus (US) a loud white noise. The resulting response suppression was assessed by a transient increase in latency of the hand movements. In control subjects, there was non-contingent CS and US presentation. The results evidenced conditioning after a single CS-US pairing. Following five preexposures to the to-be-conditioned CS, however, conditioning was abolished, seemingly expressing LI. Because a weak unconditioned response to the tone was observed after its first two presentations, an additional experiment was performed with two preexposures to the to-be-conditioned CS. With such procedure, conditioning was obtained, supporting the existence of LI in the preceding experiment. These results indicate that the present paradigm may be useful for the study of LI in human subjects, having the advantage of being similar to the experimental conditions used in the majority of LI studies in experimental animals.
Assuntos
Aprendizagem por Associação , Cognição , Condicionamento Clássico , Inibição Psicológica , Período Refratário Psicológico , Estimulação Acústica , Adulto , Feminino , Habituação Psicofisiológica , Humanos , Masculino , Modelos Psicológicos , Testes NeuropsicológicosRESUMO
The sensitivity of latent inhibition (LI) to amphetamine has been tested in humans with a paradigm close to the conditioned emotional response suppression currently used in experimental animals. The conditioned stimulus (CS) was a tone, the unconditioned stimulus (US) a strong white noise, and the response a transient delay in a regular sequence of hand movements in the resolution of the Tower of Toronto puzzle. The aim of this study was to verify whether the previously reported, disruptive effect of CS preexposure on conditioning really represents LI, by examining its sensitivity to amphetamine. Three groups of healthy volunteers received placebo, 5 or 10 mg of dexamphetamine sulphate, respectively, in a double-blind experimental design. The preexposure, conditioning and test phases were carried out under either amphetamine or placebo. The non preexposed groups treated with amphetamine were not different from the non preexposed placebo group, indicating that amphetamine did not affect conditioning. Among the preexposed groups, those receiving 10 mg of amphetamine showed normal rates of conditioning, whereas those treated with either 5 mg of amphetamine or placebo showed LI. Similar results have been reported in experimental animals. This sensitivity to amphetamine suggests that the present paradigm may be used to study LI in humans.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Dextroanfetamina/farmacologia , Inibição Psicológica , Período Refratário Psicológico , Estimulação Acústica , Adulto , Análise de Variância , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
Testing the effects of low doses of d-amphetamine on latent inhibition (LI) in two different conditioning paradigms, passive avoidance and conditioned taste aversion, provided evidence of their pharmacological equivalence. For passive avoidance, LI was expressed by the decreased latency to enter a shock compartment in preexposed rats placed 5 min in the compartment during 3 consecutive days before conditioning. In the conditioned taste aversion paradigm, a group of rats was preexposed to a solution of sucrose also for 3 consecutive days prior to the establishment of an association between sucrose and sickness elicited by an injection of LiCl. On the following day, the preexposed rats drunk more sucrose when allowed to choose between one tube containing water and an other containing sucrose. In both paradigms, 0.25 mg/kg d-amphetamine, injected daily on the 3 preexposure days and on the conditioning day, decreased LI. A dose of 0.5 mg/kg suppressed LI in the passive avoidance paradigm. The effect of a serotonergic lesion induced by i.c.v. injection of 5,7-dihydroxytryptamine (5,7-DHT) was evaluated in the same paradigms. The lesion procedure that lowered hippocampal serotonin and 5 HIAA levels by more than 80% did not affect LI. Taken together, the present results lessens the hypothesis that LI is prone to an opposing influence of the two monoaminergic systems considered in this work.
Assuntos
5,7-Di-Hidroxitriptamina/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Dextroanfetamina/farmacologia , Inibição Neural/efeitos dos fármacos , Neurotoxinas/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Mapeamento Encefálico , Relação Dose-Resposta a Droga , Eletrochoque , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos Long-Evans , Tempo de Reação/efeitos dos fármacos , Receptores Dopaminérgicos/efeitos dos fármacos , Paladar/efeitos dos fármacosRESUMO
The inferior colliculus is a primary relay for the processing of auditory information in the brainstem. The inferior colliculus is also part of the so-called brain aversion system as animals learn to switch off the electrical stimulation of this structure. The purpose of the present study was to determine whether associative learning occurs between aversion induced by electrical stimulation of the inferior colliculus and visual and auditory warning stimuli. Rats implanted with electrodes into the central nucleus of the inferior colliculus were placed inside an open-field and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle-box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold (98.12 +/- 6.15 (A, peak-to-peak) was used as negative reinforcement and light or tone as the warning stimulus. Each session consisted of 50 trials and was divided into two segments of 25 trials in order to determine the learning rate of the animals during the sessions. The rats learned to avoid the inferior colliculus stimulation when light was used as the warning stimulus (13.25 +/- 0.60 s and 8.63 +/- 0.93 s for latencies and 12.5 +/- 2.04 and 19.62 +/- 1.65 for frequencies in the first and second halves of the sessions, respectively, P < 0.01 in both cases). No significant changes in latencies (14.75 +/- 1.63 and 12.75 +/- 1.44 s) or frequencies of responses (8.75 +/- 1.20 and 11.25 +/- 1.13) were seen when tone was used as the warning stimulus (P > 0.05 in both cases). Taken together, the present results suggest that rats learn to avoid the inferior colliculus stimulation when light is used as the warning stimulus. However, this learning process does not occur when the neutral stimulus used is an acoustic one. Electrical stimulation of the inferior colliculus may disturb the signal transmission of the stimulus to be conditioned from the inferior colliculus to higher brain structures such as amygdala.
Assuntos
Percepção Auditiva/fisiologia , Aprendizagem da Esquiva/fisiologia , Colículos Inferiores/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica , Animais , Mapeamento Encefálico , Estimulação Elétrica , Masculino , Estimulação Luminosa , Ratos , Ratos WistarRESUMO
The inferior colliculus is a primary relay for the processing of auditory information in the brainstem. The inferior colluculus is also part of the so-called brain aversion system as animals learn to switch off the electrical stimulation of this structure. The purpose of the present study was to determine whether associative learning occurs between aversion induced by electrical stimulation of the inferior colliculus and visual and auditory warning stimuli. Rats implanted with electrodes into the central nucleus of the inferior colliculus were placed inside an open-field and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle-box and submitted to a two-way avoidance pardigm. Electrical stimulation of the inferior colliculus at the escape threshold (98.12 + 6.15 (A, peak-to-peak) was used as negative reinforcement and light or tone as the warning stimulus. Each session consisted of 50 trials and was divided into two segments of 25 trials in order to determine the learning rate of the animals during the sessions. The rats learned to avoid the inferior colliculus stimulation when light was used as the warning stimulus (13.25 + 0.60 s and 8.63 + 0.93 for lactencies and 12.5 + 2.04 and 19.62 + 1.65 frequencies in the first and second halves of the sessions, respectively, P<0.01 in both cases). No significant changes in latencies (14.75 + 1.63 and 12.75 + 1.44 s) or frequencies of responses (8.75 + 1.20 and 11.25 + 1.13) were seen when tone was used as the warning stimulus (P>0.05 in both cases). Taken together, the present results suggest that rats learn to avoid the inferior colliculus stimulation when light is used as the warning stimulus. However, this learning process does not occur when the neutral stimulus used is an acoustic one. Electrical stimulation of the inferior colliculus may disturb the signal transmission of the stimulus to be conditioned from the inferior colliculus to higher brain structures such as amygdala.
Assuntos
Animais , Masculino , Ratos , Percepção Auditiva/fisiologia , Aprendizagem da Esquiva/fisiologia , Colículos Inferiores/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica , Mapeamento Encefálico , Estimulação Elétrica , Estimulação Luminosa , Ratos WistarRESUMO
Latent inhibition consists of a retardation of conditioning seen when the to be conditioned stimulus is presented a number of times with no other consequence. This phenomenon likely reflects processes of selective attention whereby irrelevant stimuli come to be ignored. Using physiological models for auditory attention, some investigators have suggested that selective attention acts as a filtering mechanism capable of inhibiting or gating unattended stimuli relative to attended ones in the auditory cortex. In the present work, an on-baseline conditioned suppression response procedure was used to study the effects of stimulus preexposure in rats submitted to bilateral auditory cortex ablation. Our results indicate that both auditory cortex lesioned and control animals exhibit latent inhibition to a sound. However, learning after preexposure to that sound was particularly slow in animals with bilateral auditory cortex lesion, i.e. in these animals, the latent inhibition effect appeared to be enhanced. Conditioning from one day to the next also varied slightly. Thus, the auditory cortex appears to modulate learning when the conditioned stimulus is a sound.
Assuntos
Córtex Auditivo/fisiologia , Emoções/fisiologia , Reflexo de Sobressalto/fisiologia , Estimulação Acústica , Animais , Atenção/fisiologia , Córtex Auditivo/anatomia & histologia , Condicionamento Operante/fisiologia , Masculino , Ratos , Privação de Água/fisiologiaRESUMO
The inferior colliculus has been implicated in aversive or anxiogenic aspects of defensive behavior. Animals learn to turn off electrical stimulation applied to the inferior colliculus. The purpose of the present study was to determine (1) whether this aversion induced by electrical stimulation can be conditioned to a conditioned stimulus (CS, light) and (2) whether pre-exposure to the CS will diminish the extent of such conditioning, i.e. whether latent inhibition can be established with this paradigm. Rats were placed inside an open field, and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold was used as negative reinforcement and shuttle box illumination as the CS. The rats quickly learned to avoid or terminate the inferior-colliculus stimulation. Furthermore, the performance of the animals in this paradigm was significantly disrupted when they were pre-exposed to 50 presentations of the CS before the session. These data suggest that the inferior colliculus has neural substrates for supporting associative learning and latent inhibition.
Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Colículos Inferiores/fisiologia , Motivação , Inibição Neural/fisiologia , Reforço Psicológico , Animais , Nível de Alerta/fisiologia , Aprendizagem por Associação/fisiologia , Mapeamento Encefálico , Estimulação Elétrica , Reação de Fuga/fisiologia , Masculino , Ratos , Ratos Wistar , Limiar Sensorial/fisiologiaRESUMO
c-fos immunoreactivity was used to map brain areas in which neurons reacted either to electrical stimulation or to microinjection of the excitatory amino acid kainate and of the GABAA antagonist, SR-95531, applied to the medial hypothalamus of freely moving rats. All these stimulations induced flight behavior of moderate intensity. Immunoreactive cells were found within a radius of 0.5 mm around the stimulated area. Distally, clusters of labeled cells were found ipsilaterally in the piriform and entorhinal cortices, in several amygdaloid nuclei, in the bed nucleus of the stria terminalis, in the septo-hypothalamic nucleus, in the paraventricular, anterior and dorsomedial hypothalamic nuclei, the the paraventricular thalamic nucleus, in the dorsal periaqueductal gray extending to the cuneiform nucleus, and bilaterally in the supramammillary decussation and the locus coeruleus. The specificity of the brain areas thus labeled was indicated by the unilateral pattern of activation as well as by the different pattern obtained after control microinjection of saline. Therefore, these results are likely to provide sound information about the brain structures involved in defensive-aversive behavior evoked from the medial hypothalamus.
Assuntos
Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Hipotálamo Médio/efeitos dos fármacos , Hipotálamo Médio/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Mapeamento Encefálico , Estimulação Elétrica , Antagonistas de Receptores de GABA-A , Hipotálamo Médio/citologia , Imuno-Histoquímica , Ácido Caínico/farmacologia , Masculino , Piridazinas/farmacologia , Ratos , Estimulação QuímicaRESUMO
Fos protein immunohistochemistry was used to identify the neural substrate of fear/anxiety. The structures activated by exposure of Long Evans male rats (280-300 g) to the elevated plus-maze, a widely used animal model of anxiety, were compared with those activated by chemical stimulation of two aversive areas of the brain, the dorsal periaqueductal gray matter and the medial hypothalamus. Three different patterns of activation were obtained: Pattern 1 resulted from microinjection of the excitatory amino acid kainate (60 pmol; N = 5) or of the GABA(A) receptor antagonist SR-95531 (16 pmol; N = 3) into the dorsal periaqueductal gray matter and consisted mainly of caudal structures; Pattern 2 was observed after kainate injection (60 pmol; N = 4) into the medial hypothalamus and had a predominantly prosencephalic distribution; Pattern 3 extended from rostral to caudal brain regions and was induced by microinjection of either SR-95531 (16 pmol; N = 1) or kainate (120 pmol; N = 3) into the medial hypothalamus, as well as by 15-min exposure to the plus-maze (N = 3). Control animals were either injected with saline into the MH (N = 3) or the PAG (N = 3) or were exposed for 15 s to the elevated plus maze (N = 3) and exhibited no significant labeling. These results further support the participation of periventricular structures in the regulation of fear and aversion.
Assuntos
Medo/fisiologia , Hipotálamo Médio/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Proteínas Proto-Oncogênicas c-fos/fisiologia , Animais , Ansiedade , Medo/efeitos dos fármacos , Hipotálamo Médio/efeitos dos fármacos , Imuno-Histoquímica , Ácido Caínico/farmacologia , Masculino , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Piridazinas/farmacologia , Ratos , Fatores de TempoRESUMO
Fos protein immunohistochemistry was used to identify the neural substrate of fear/anxiety. The structures activated by exposure of Long Evans male rats (280-300 g) to the elevated plus-maze, a widely used animal model of anxiety, were compared with those activated by chemical stimulation of two aversive areas of the brain, the dorsal periaqueductal gray matter and the medial hypothalamus. Three different patterns of activation were obtained: Pattern 1 resulted from microinjection of the excitatory amino acid kainate (60 pmol; N = 5) or of the GABA(A) receptor antagonist SR-95531 (16 pmol; N = 3) into the dorsal periaqueductal gray matter and consisted mainly of caudal structures; Pattern 2 was observed after kainate injection (60 pmol; N = 4) into the medial hypothalamus and had a predominantly prosencephalic distribution; Pattern 3 extended from rostral to caudal brain regions and was induced by microinjection of either SR-95531 (16 pmol; N = 1) or kainate (120 pmol; N = 3) into the medial hypothalamus, as well as by 15-min exposure to the plus-maze (N = 3). Control animals were either injected with saline into the MH (N = 3) or the PAG (N = 3) or were exposed for 15 s to the elevated plus maze (N = 3) and exhibited no significant labeling. These results further support the participation of periventricular structures in the regulation of fear and aversion.
Assuntos
Animais , Masculino , Ratos , Medo , Hipotálamo Médio/fisiologia , Proteínas Proto-Oncogênicas c-fos/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ácido Caínico/farmacologia , Ansiedade , Medo , Hipotálamo Médio/efeitos dos fármacos , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Piridazinas , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Fatores de TempoRESUMO
The Fos protein immunohistochemistry technique was used to map the brain areas activated by a 15-min exposure of rats to the elevated plus maze, an ethologically based animal model of anxiety. Two hours after the test, labeling was found mainly in the piriform and entorhinal cortices, amygdala, midline thalamic nuclei, several medial hypothalamic nuclei, periaqueductal gray matter, superior and inferior colliculus, cuneiform nucleus, dorsal raphe nucleus and locus coeruleus. These results support a participation of these structures in anxiety.