Differential actions of classical and atypical neuroleptics on mouse nigrostriatal neurons

1. 1. The classical neuroleptics haloperidol, perphenazine and chlorpromazine increase both dopamine metabolism and release in the mouse striatum.

2. 2. The atypical agents clozapine and thioridazine increase dopamine metabolism with no increase in release.

3. 3. At high doses, sulpiride increases both dopamine metabolism and release.

4. 4. These data suggest that atypical neuroleptics act to inhibit dopamine release and indicate that sulpiride may not be an atypical agent.

Experiences of a methadone detoxification programme for opium addicts.

The conduction of a new programme of methadone detoxification of opium addicts in a general hospital setting is described. A blind technique of dispensing methadone in a powdered form mixed with powdered aspirin to two groups of opium addicts was used: Group A were given a gradual reduction of the methadone over a period of ten days, while group B were maintained on the initial stabilising dose for the ten days and then abruptly withdrawn from methadone on the eleventh day. It was observed that the number of complaints and abstinence symptoms was markedly reduced in Group B. It is suggested that this technique is a major improvement over the standard progressive reduction method of methadone detoxification. A follow-up of these patients over a period of 1 1/2 years is reported.     

Discriminative stimulus properties of a small dose of cocaine

This study characterized the interoceptive discriminative stimulus (IDS) produced by a small dose of cocaine. Rats were trained to use a dose of cocaine of 1.25 mg/kg vs saline as the basis for choosing one of two levers for food reinforcement on a fixed ratio 10 schedule. The discrimination was acquired over approx. 60 training sessions. d-Amphetamine generalized to cocaine with approximately equal potency (ED₅₀'s for cocaine and d-amphetamine were 0.07 and 0.06 mg/kg, respectively); 20 mg/kg cocaine and 10 mg/kg methylphenidate also generalized to the cocaine lever. Pentylenetetrazol, 20 mg/kg, did not generalize to the cocaine lever, and diazepam, 10 mg/kg, did not block the 1.25 mg/kg cocaine discrimination. These data indicate that when a small dose of cocaine is used as the basis of discrimination training, the discriminative stimulus that it produces is qualitatively and quantitatively similar to that produced by small doses of amphetamine, is still discriminated with a large dose of cocaine, and is dissimilar to the discriminative stimulus produced by pentylenetetrazol.     

45Ca uptake from water by snails (Lymnaea vulgaris) in control and detergent-polluted samples

A biostatic assay method involving 45Ca uptake into shells and tissues of snails (Lymnaea vulgaris) in 72 hr was developed to follow the effect of detergent-polluted water on ecosystems. There was a marked decrease in the 45Ca uptake by shells and tissues of linear alkyl benzene sulfonate-exposed animals as compared to controls. No change in 45Ca uptake was observed in dead shells, thereby excluding the possibility of passive exchange.     

Inhibition of hepatic hexobarbital metabolism by dextro amphetamine

Summary In mice, d-amphetamine injected intraperitoneally (10 mg/kg, 1 hr before sacrifice) decreased in vitro hepatic metabolism of hexobarbital. Since the addition of d-amphetamine to liver homogenates in vitro also inhibited the hexobarbital metabolism, the in vivo effect of amphetamine was not due to its pharmacodynamic action.     

Effect of alloxan on β-cells of islets of langerhans in the albino rat

Summary 1) The diabetogenic dose of alloxan for the albino rat is 150 mg/kg body weight, given in a single dose, subcutaneously. 2) When one third of the diabetogenic dose is employed, albino rats fail to develop diabetes and the pancreatic islet tissue does not show any change revealed by light microscopy. 3) Administration of subdiabetogenic doses of alloxan concurrently with glucose, ACTH or anterior pituitary extract results in structural changes in the pancreatic islet tissue which are reflected by changes in the blood-sugar levels. 4) The histological changes observed in the islet tissue of the pancreases are: degranulation, hyaline degeneration, «hydropic» changes and necrosis. «Hydropic» changes are found to be due to glycogen infiltration of the cells.

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Zusammenfassung 1) Die diabetogene Alloxan-Dosis fuer die Albinoratte betraegt 150 mg/kg in Einzeldosis auf subkutanem Weg. 2) Wenn man ein Drittel der diabetogenen Dosis verwendet, offenbaren die Albinoratten keinen Diabetes und das inselpankreatische Gewebe zeigt keine mit dem optischen Mikroskop erfassbare Veraenderung. 3) Die Verabreichung von subdiabetogenen Alloxan-Dosen, zusammen mit Glukose, ACTH oder Hypophysenvorderlappen-Extrakt bewirkt strukturelle Veraenderungen im Pankreas-Inselgewebe, die ihren Widerhall in Blutzuckerschwankungen finden. 4) Die im Pankreas-Inselgewebe beobachteten histologischen Veraenderungen sind: Degranulierung, hyaline Degeneration, «hydropische» Veraenderungen und Nekrosen. Die «hydropischen» Veraenderungen werden durch die Glykogen-Infiltration in die Zellen verursacht.

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Resumen 1) La dosis diabetógena de aloxana para la rata albina es de 150 mg/kg, suministrados en dosis única por vía subcutánea. 2) Cuando se emplea la tercera parte de la dosis diabetógena, las ratas albinas no desarrollan la diábetes y el tejido ínsulo-pancreático no presenta ninguna alteración apreciable al microscopio óptico. 3) La suministración de dosis sub-diabetógenas de aloxana, conjuntamente con la glucosa, el ACTH o el extracto de antehipófisis, produce alteraciones de la estructura en el tejido de las islas del páncreas: dichas alteraciones se evidencian con las variaciones de la glucemia. 4) Las alteraciones histológicas observadas en el tejido insular del páncreas son las siguientes: degranulación, degeneración hialina, alteraciones «hidrópicas» y necrosis. Las alteraciones «hidrópicas» son consecuencia de infiltración de glúcogeno en las células.

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Resume 1) La dose diabétogène de alloxane pour le rat albinos est de 150 mg/kg administrée dans une seule dose par voie subcutanée. 2) En employant un tiers de la dose diabétogène, les rats albinos ne développent pas le diabète et le tissue insulo-pancréatique ne présente pas des altérations relevables au microscope optique. 3) L'administration de doses subdiabétogènes de alloxane, avec du glucose, ACTH ou extrait de antéhypophyse, provoque des altérations dans le tissue des îles du pancréas avec des variations de la glycémie. 4) Les altérations histologiques observées dans le tissue insulaire du pancréas sont: dégranulation, dégénération jaline, altérations «hydropiques» et nécrose. Les altérations «hydropiques» sont dues à l'infiltration du glycogène dans les cellules.

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Riassunto 1) La dose diabetogena di allossana per il ratto albino è di 150 mg/kg somministrati in una dose singola per via sottocutanea. 2) Quando si impiega un terzo della dose diabetogena, i ratti albini non sviluppano il diabete ed il tessuto insulopancreatico non presenta alcuna alterazione rilevabile al microscopio ottico. 3) La somministrazione di dosi subdiabetogene di allossana, in concomitanza con il glucosio, l'ACTH o l'estratto di anteipofisi, determina alterazioni strutturali nel tessuto delle isole del pancreas che sono riflesse da variazioni della glicemia. 4) Le alterazioni istologiche osservate nel tessuto insulare del pancreas sono: degranulazione, degenerazione jalina, alterazioni «idropiche» e necrosi. Le alterazioni «idropiche» sono dovute all'infiltrazione del glicogeno nelle cellule.

     

Effect of acute and chronic pentylenetetrazol treatment on benzodiazepine and cholinergic receptor binding in rat brain

The binding of [3H] diazepam and [3H] flunitrazepam in rat cerebral cortex was not altered by either acute or chronic administration of pentylenetetrazol except in rats made to convulse 30 min before sacrifice. Rats treated for up to 6 months with doses of pentylenetetrazol which are below seizure threshold in naive rats, became increasingly sensitive to the CNS stimulant effect of pentylenetetrazol as demonstrated by the development of myoclonus and convulsions during treatment periods. These effects were not correlated with any changes in benzodiazepine binding in cerebral cortex or cerebellum and [3H] quinuclidinyl benzilate binding in cerebral cortex. Acute convulsant doses of pentylenetetrazol increased benzodiazepine binding in cerebral cortex, but only in those rats which actively convulsed. Benzodiazepine and cholinergic receptors of the cortex, and benzodiazepine receptors of the cerebellum, therefore, do not appear to change with either the acute or chronic subconvulsive administration of pentylenetetrazol.