[The placebo effect: between mind and brain].
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Animals↗
Biomedical subjects
E Burunat
Publications and source records attributed to E Burunat.
Gonadal influences on behavioral deterioration with aging of male rats.
There is much evidence that gonadal steroids modulate brain and behavioral development. However their possible influence on age-related deteroriation of brain and behavior has received little attention. We now present evidence that neonatal castration reduces the decline in locomotion, motor coordination, and circadian activity rhythms that normally accompanies old age in male rats. Three behavioral tests (open field, Rota-Rod, and wheel running) were conducted with aged male rats (24 months). Those castrated in the first 24 hr of postnatal life were more active in the open field (P less than 0.001) than aged rats that were sham-operated neonatally. The sham-operated aged males showed a more marked deterioration of motor coordination in the Rota-Rod (P less than 0.01) and greater disorganization of circadian wheel-running (P less than 0.05) than the neonatal castrates or than young rats neonatally sham-operated.
Aging↗
Conditioning of the early behavioral response to apomorphine in the rotational model of Parkinson's disease.
The rotational model of Parkinson's disease has been widely used to investigate the action of dopamine agonists. This animal model involves the production of a unilateral nigrostriatal lesion in rats. The lesion is produced with 6-hydroxydopamine which causes dopamine depletion and subsequent supersensitivity of striatal receptors. Thus, administration of drugs which are therapeutically effective in Parkinson's disease, elicits circling behavior contralateral to the lesioned side. The origin of the paradoxical response and the undrugged rotations observed after saline injections in apomorphine pretreated rats has not been explained. We report here that the undrugged response can be associated with the early rotational response elicited by the drug. Furthermore, we show the effect of inhibitory conditioning on this early response. Our results suggest that pharmacological conditioning plays a significant role in the modification of the therapeutic effectiveness of CNS-active drugs after extended treatments.
Animals↗
Conditioned response to apomorphine in nigro-striatal system-lesioned rats: the origin of undrugged rotational response.
Development and time-course characteristics of Early rotational response (ER) to apomorphine in 6-hydroxydopamine-lesioned rats is explored. We show here how this ER can be considered a conditioned response that arises when the drug is repeatedly administered, according to a classical conditioning paradigm. In this way, the ER to apomorphine can be considered a non-pharmacological, conditioned, placebo response, the drug action being the unconditioned stimulus (UCS). In our model, the undrugged rotational response elicited by saline injections two weeks after drug treatment can be considered as the conditioned response (CR) to the conditioned stimulus, the CS being the environment associated with the drug treatment. This CR had not previously been identified during the drug treatment. Thus, we studied the acquisition of the ER, nonexistent after the first injection of apomorphine. Furthermore, we distinguish between this ER and the later, strictly pharmacological rotational response (LR) to apomorphine. Finally, we related this ER to the undrugged, paradoxical response to saline. In conclusion, we demonstrate the paradigm of pharmacological conditioning using this animal model of Parkinson's disease, supported by our own results and those of Silverman and Ho (1981).
Animals↗
Undrugged rotational response in nigro-striatal system-lesioned rats is related to the previous early response to apomorphine when repeatedly administered.
Development and time-course characteristics of undrugged rotational response weeks or months after repeated apomorphine administration in 6-hydroxydopamine-lesioned rats were explored. In one series of experiments, all groups received several drug doses two-three weeks post-lesion and remained undrugged at different intervals from the last drug injection. Weeks or months later, they were injected with saline in the same environment where they previously had received apomorphine. In this way we studied acquisition, time-course and extinction of the rotational response after saline. Furthermore, we related this undrugged response which does not fully develop until two weeks after treatment, and which previously had not been related to a specific parameter of the rotational response to the drug, to a critical point of the time-course response to the drug, i.e., the early rotational response in the first minute after injection. This early response is a learning phenomenon based on the environmental cues where drug has been repeatedly administered. Finally, we state the concept of pharmacological conditioning using this animal model of Parkinson's disease, in agreement with our own results and the previous results of Silverman and Ho (1981).
Animals↗
Conditioning the placebo response in the rotational model of Parkinson's disease.
Persistent behavioural effect of the direct dopamine receptors agonist apomorphine in the rotational model of Parkinson's disease was investigated. We show how this placebo response can be considered an extraordinary example of environment-drug associative learning and how it can be related to a critical point of the time-course response to the drug after repeated administration. Classical conditioning of "placebo response" in an animal model of a neurological or psychiatric disease had not been reported previously.
Animals↗