Avaliação do estado emocional associado à catalepsia causada pela administração intraperitoneal de haloperidol

Haloperidol is a dopamine receptor antagonist used to treat schizophrenia. When systemically administered in rodents, haloperidol induces catalepsy, a state of immobility very similar to that seen in Parkinson's disease. It is known that many of Parkinson's disease symptoms are dependent on the emotional state since patients are still able to respond to external triggers such as loud noise or visual signaling. Recent data highlighted the importance of glutamatergic neurotransmission in the inferior colliculus (IC) on the cataleptic state induced by haloperidol in rats. Given the importance of IC in the brain aversion system and its connections to motor pathways, and based on the clinical reports of the emotional influence on the motor aspect of Parkinson's disease, the objective of the present study was to evaluate the emotional aspect related to catalepsy induced by intraperitoneal administration of haloperidol. To this end, we analysed ultrasonic vocalizations (UVs) of 22 kHz (indicative of aversion) in rats during the tests of catalepsy, open field and contextual conditioned fear. Systemic administration of haloperidol affected the motor activity, inducing catalepsy and decreasing exploratory activity in the open field. There were no UVs of 22 kHz resulting from treatment with haloperidol in catalepsy or open field tests. In the contextual conditioned fear test, haloperidol increased freezing when administered before the test, but decreased freezing on test day when administered before training. In this same test, haloperidol decreased the UVs on the day it was administered (training or test). The catalepsy induced by systemic administration of haloperidol seems to have also affected the motor aspect of UVs. In this way, it was not possible to clarify the existence of an aversive emotional state associated haloperidol induced catalepsy

Involvement of dopamine receptors in diethylpropion-induced conditioning place preference

Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N = 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 ± 39 vs 565 ± 48 s). Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg, sc) 10 min before DEP (15 mg/kg, ip) blocked DEP-induced CPP (418 ± 37 vs 389 ± 31 s) while haloperidol (0.5 mg/kg, ip), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 ± 36 vs 536 ± 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DEP

Actions of angiotensin II and dopamine in the medial preoptic area on prolactin secretion

Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectornized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of da antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and da actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of da through D-2 receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of da through D, receptors and in other part by inhibition of stimulatory action of da through D2 receptors.

Experiência clínica com o uso de sedativos em terapia intensiva: estudo retrospectivo

JUSTIFICATIVA E OBJETIVOS: Dentre as indicações mais freqüentes de sedação em pacientes internados em Unidades de Terapia Intensiva (UTI) estão a instituição e a manutenção de ventilação artificial, a ansiedade e procedimentos desconfortáveis ou dolorosos. O objetivo deste estudo retrospectivo foi verificar as indicações e as técnicas mais comuns de sedação em pacientes graves internados na Unidade de Terapia Intensiva Cirúrgica da Escola Paulista de Medicina (EPM/UNIFESP) durante um período de 11 meses. MÉTODO: Após terem sido excluídos os pacientes que permaneceram na UTI menos de 24 horas ou estavam sem exames indispensáveis para o cálculo do índice de gravidade (APACHE II), a amostra ficou reduzida a 307 pacientes. Foram analisadas as técnicas mais utilizadas, as indicações de sedação e a associação de bloqueadores neuromusculares. RESULTADOS: A sedação foi administrada em 37,4% dos pacientes. Entre as indicações de sedação estão os distúrbios de natureza psiquiátrica, como delírio, agitação, medo e ansiedade. Estas corresponderam a 25,77% de todas as indicações. A maioria dos pacientes ventilados artificialmente também necessita de sedativos. Instalação e manutenção de ventilação mecânica corresponderam à maioria das indicações, em torno de 57,73% dentre os pacientes sedados. Procedimentos como intubação traqueal e broncoscopia tiveram 11,34% das indicações e controle do metabolismo (coma barbitúrico e tétano), 5,15%. As técnicas mais comumente utilizadas incluíram opióides isolados ou associados a benzodiazepínicos. Neste estudo, o fentanil foi utilizado em 58% das técnicas, isoladamente, e em 21,64% associado ao midazolam. Haloperidol, diazepam, propofol e tiopental somaram 19,5%. Bloqueadores neuromusculares foram utilizados em 22,7% dos casos em pacientes ventilados artificialmente. CONCLUSÕES: A sedação é recurso terapêutico freqüente em Terapia Intensiva, comumente utilizada para facilitar a ventilação artificial e tratar os problemas de natureza psiquiátrica. Fentanil, isoladamente ou em associação com midazolam, foi o agente mais utilizado.

Envolvimento do sistema dopaminérgico na sensibilização comportamental ao femproporex

The effects of repeated administration of fenproporex (FEN) on motor activity of rats were studied. FEN-treated group (5.0 mg/kg, i.p., single dose, 7 consecutive days), showed a marked increase in the motor activity of rats, indicating that the drug induced behavioral sensitization. Repeated coadministration of haloperidol prevented the development of sensitization to repeated administration of FEN. Repeated administration of FEN increased also locomotor activity measured in the open field, ratifying the occurence of sensitization. These findings indicated development of sensitization to repeated FEN administration and that the dopamine system might be involved in the mechanism of sensitization.