RESUMEN
The writings of Franco Basaglia are critically reviewed, both from a technical psychiatric point of view and from a general political and social one. Basaglia maintained that the causes of psychiatric disorder are essentially social in nature, and that the only valid treatments are political struggle and the revival of the patient's aggressiveness. Therefore, no institution can be therapeutic for the patient, since its aim must be his custody and violent destruction. These statements are considered in the light of the need for institutions which are a therapeutic alternative to the mental hospital. Basaglia's 'liberal' defence of the individual against society is analysed, in relation to the negative consequences that the Italian Law 180 of 1978 is having on the care of long-term psychiatric patients. This law 'forgot' such patients, as well as adversely affecting the treatment of acute patients, for whom an insufficient number of psychiatric beds was permitted in general hospitals. A revision is proposed of Law 180 that would make possible the setting up of alternative institutions to outdated mental hospitals, but at the same time allow a transformation of their old structures.
Asunto(s)
Institucionalización , Psiquiatría/historia , Economía , Historia del Siglo XX , Humanos , Italia , Legislación como Asunto , Trastornos Mentales/etiología , Trastornos Mentales/terapia , Política , Clase Social , Condiciones Sociales , Predominio Social , ViolenciaRESUMEN
Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nerve function, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments ['newly synthesized' (NS) and 'main storage'] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA.
Asunto(s)
Encéfalo/metabolismo , Catecolaminas/metabolismo , Animales , Conducta/fisiología , Dopamina/metabolismo , Norepinefrina/metabolismo , Ratas , Transmisión SinápticaRESUMEN
The penetration and distribution in various areas of cat brain of 14C-DL-DOPA and/or its derivatives was studied by the autoradiographic technique. The highest activity was found, 1 hr after administration, in the caudate nucleus, putamen and n. accumbens, while hypothalamus, substantia nigra, substantia grisea pericentralis, tuberculum olfactorium, raphe nuclei and nucleus interpeduncolaris showed lower levels of labelling. Very low activity was detected in the cerebral cortex and in the other gray and white matter structures of brain. After pretreatment with a peripheral DOPA-decarboxylase inhibitor or high dosage of cold DOPA, the distribution pattern was not modified but the levels of radioactivity were greatly enhanced. The localization of the drug in dopaminergic structures and other areas of the brain is discussed.
Asunto(s)
Encéfalo/metabolismo , Dihidroxifenilalanina/metabolismo , Animales , Autorradiografía , Benserazida/farmacología , Encéfalo/anatomía & histología , Química Encefálica/efectos de los fármacos , Gatos , MasculinoRESUMEN
Acute morphine induced a dose-dependent hypokinesia and rigidity, but only mild and non-dose-dependent catalepsy. AMT, injected 1/2 h after morphine, slightly potentiated catalepsy but not hypokinesia during 3 h after morphine; in contrast, rigidity was decreased. The behavioral changes induced by AMT were accelerated in onset and reached their usual development, although AMT toxicity and hypothermia were completely antagonized; thus, it would appear that AMT hypokinesia/catalepsy are not the consequence of toxicity. When morphine was injected 4 h after AMT, a mutual potentiation of the two drugs on hypokinesia and catalepsy was observed, although previous biochemical measurements had shown no effect of morphine on CA depletion under these conditions. Rigidity appeared to be antagonized. After 17 days of repeated injections, morphine no longer elicited hypokinesia and catalepsy, but no cross-tolerance developed to the AMT behavioral changes. A similar lack of cross-tolerance to the effects of AMT or haloperidol was observed when morphine tolerance was induced by pellet implantation. Catalepsy and hypokinesia developed in a much more pronounced way after two large i.p. doses than after small, multiple administration of AMT; this difference was accompanied by a significantly lower concentration of brain DA, but not NA in the former group. The hyperthermic response observed after a 40 mg/kg s.c. injection of morphine was reversed to hypothermia when the same dose was given 4 or 10 h after CA synthesis inhibition. Cocaine strongly antagonized AMT hypokinesia and catalepsy when given 8 1/2 h after AMT, and, although to a lesser extent, even when injected 12 1/2 h after AMT.
Asunto(s)
Catalepsia/inducido químicamente , Cocaína/farmacología , Metiltirosinas/farmacología , Morfina/farmacología , Trastornos Psicomotores/inducido químicamente , Animales , Temperatura Corporal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Catecolaminas/análisis , Interacciones Farmacológicas , Tolerancia a Medicamentos , Haloperidol/farmacología , Humanos , Masculino , RatasRESUMEN
The effects of different manipulations of brain serotonin (5-HT) content on the development of morphine dependence were investigated in rats, which were implanted with morphine pellets for 40 days. Serotonin content was decreased by (a) short or long term inhibition of tryptophan hydroxylase with para-chlorophenylalanine (PCPA), (b) by short or long term degeneration of 5-HT containing nerve terminals with 5,6-dihydroxytryptamine or (c) by degeneration of 5-HT containing nerve terminals by lesioning of midbrain raphe nuclei. With all methods used, the frequency of withdrawal jumping was significantly reduced, while other withdrawal signs remained more or less unchanged. Additional administration of 5-HTP to chronically PCPA treated rats did not reverse the PCPA effect. Since chronic reduction of 5-HT level during the whole time of morphine exposure changed withdrawal symptomatology in nearly the same way as did a decrease in 5-HT level during the time of withdrawal only, it is suggested that serotonergic mechanisms are not linked to the basic processes underlying dependence development but that they are only involved in the nervous pathways mediating the expression of some withdrawal signs.
Asunto(s)
Dependencia de Morfina/fisiopatología , Serotonina/fisiología , 5,6-Dihidroxitriptamina/farmacología , Animales , Química Encefálica/efectos de los fármacos , Ciproheptadina/farmacología , Fenclonina/farmacología , Humanos , Inyecciones Intraventriculares , Masculino , Mesencéfalo/fisiología , Morfina/administración & dosificación , Vías Nerviosas/fisiología , Norepinefrina/metabolismo , Ratas , Serotonina/metabolismo , Síndrome de Abstinencia a Sustancias/fisiopatologíaRESUMEN
Morphine increased the rate of brain dopamine (DA) depletion when given before alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide, but not when given after AMT. No effect of morphine was found on the rate of depletion of brain noradrenaline (NA) or serotonin (5-HT) after the two synthesis inhibitors. The accumulation of homovanillic acid and 5-hydroxy-indoleacetic acid induced by probenecid was significantly increased by morphine pretreatment, whereas the accumulation of 3-methoxy-4-hydroxy-phenylglycol sulphate was not changed. These findings can be best explained by the hypothesis that morphine increases the non-functional intraneuronal catabolism of newly synthesized DA and 5-HT, without much effect on the monoamines already taken up in the synaptic vesicles. NA turnover does not seem to be changed by acute morphine administration.
Asunto(s)
Encéfalo/metabolismo , Catecolaminas/metabolismo , Morfina/farmacología , Serotonina/metabolismo , 3-Metoxi-4-hidroxifenil Etanol/metabolismo , Animales , Transporte Biológico Activo/efectos de los fármacos , Encéfalo/efectos de los fármacos , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Metiltirosinas/farmacología , Morfina/administración & dosificación , Norepinefrina/metabolismo , Probenecid/farmacología , Ratas , Factores de TiempoRESUMEN
The turnover of brain monoamine was studied in rats in which different degrees of tolerance to and dependence on morphine were induced by pellet implantation. The degree of tolerance to morphine was assessed by measuring the increase in effective dose for an antinociceptive effect (vocalization test). The rate of depletion of brain dopamine (DA) and serotonin (5-ht) after alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide (dopacetamide) was not changed by chronic morphine treatment. In contrast, the accumulation of brain homovanillic acid HVA) and 5-hydroxyindoleacetic acid (5-HIAA) after probenecid was significantly increased, but there was no correlation between the biochemical changes and the degree of tolerance/dependence of the animals; at a very high degree of dependence 5-HIAA accumulation even became normal. In rats in which smaller amounts of morphine were repeatedly injected every 8 hr for 1 week the increased accumulation of HVA and 5-HIAA persisted in spite of complete tolerance to the antinociceptive effect. The rate of depletion of brain noradrenaline (NA) after AMT or dopacetamide was not changed and the accumulation of brain 3-methoxy-4-hydroxy-phenylglycol sulphate (MHPG-SO4) after probenecid was not affected in most chronic morphine groups. In the group with the highest degree of tolerance/dependence NA depletion after AMT was even retarded. The results suggest that chronic morphine treatment increases the synthesis and the intraneuronal destruction of newly synthesized DA and 5-HT without changing the rate of functional utilization of the monoamines. It is unlikely that the changes in monoamine metabolism are causally related to processes leading to morphine tolerance/dependence.
Asunto(s)
Encéfalo/metabolismo , Catecolaminas/metabolismo , Morfina/farmacología , Serotonina/metabolismo , 3-Metoxi-4-hidroxifenil Etanol/metabolismo , Animales , Encéfalo/efectos de los fármacos , Dopamina/metabolismo , Implantes de Medicamentos , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Masculino , Metiltirosinas/farmacología , Morfina/administración & dosificación , Norepinefrina/metabolismo , Ratas , Factores de Tiempo , Vocalización Animal/efectos de los fármacosRESUMEN
Yohimbine moderately increased the depletion of brain dopamine (DA) after alpha-methyl-p-tyrosine (AMT) only when the two drugs were given at the same time; the baseline concentration of brain homovanillic acid (HVA) and its accumulation after probenecid were strongly increased by yohimbine. Yohimbine markedly decreased the concentration of brain noradrenaline (NA), both when given alone and before or at the same time as AMT; when it was given at an increasing interval after AMT, the effect became progressively smaller. The baseline concentration of brain 3-methyoxy-4-hydroxyphenylethyleneglycol sulphate and its accumulation after probenecid were increased by yohimbine; this effect was not as marked as that on HVA and was proportional to the quantity of NA depleted in the Amt method. The accumulation of brain k-hydroxyindoleacetic acid after probenecid was decreased by yohimbine pretreatment.