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S Lazareno

Publications and source records attributed to S Lazareno.

40 records · Page 3Linked to original sources

Selective labelling of dopamine (D2) receptors in rat striatum by [3H]domperidone but not by [3H]spiperone.

Specific binding of [3H]spiperone and [3H]domperidone, displaceable by 1 microM d-butaclamol, was examined in rat striatal membranes. Initial saturation and displacement experiments indicated that [3H]spiperone bound to more sites than [3H]domperidone and that, whilst all displacing drugs were more potent against [3H]domperidone, this difference in potency was greatest for dopamine agonists and specific antagonists and least for 5HT-related drugs. Sulpiride displaced [3H]spiperone biphasically, and was used at a concentration of 50 microM to examine two classes of [3H]spiperone binding: site 1 displaceable by sulpiride, and site 2 displaceable by butaclamol but not by sulpiride. Site 1 had twice the capacity of site 2 and ten times the affinity for [3H]spiperone. Dopaminergic drugs displaced preferentially from site 1, whilst 5HT-related drugs were more potent against site 2. GTP reduced the potency of dopamine, noradrenaline and, to a lesser extent, 5HT at site 1, but had no effect at site 2. [3H]Domperidone sites had the same capacity as [3H]spiperone site 1, and dopamine, noradrenaline and 5HT, in the absence or presence of GTP, and sulpiride had essentially identical affinities for [3H]domperidone sites and [3H]spiperone site 1. It is concluded that [3H]domperidone and [3H]spiperone label an identical population of dopamine (D2) receptors, whilst [3H]spiperone also labels a substantial number of non-dopamine sites, at least some of which are 5HT-related. [3H]spiperone also labels a substantial number of non-dopamine sites, at least some of which are 5HT-related. [3H]Domperidone is the better radioligand for dopamine receptors.

Animals↗

d-Amphetamine and punished responding: the role of catecholamines and anorexia.

Rats were trained to press a lever for food on a schedule in which components of variable interval reinforcement (V12') alternated with conflict components in which every response resulted in food delivery and footshock. Low doses of d-amphetamine selectively suppressed responding in the conflict component in a dose-dependent manner, whereas prefeeding suppressed responding in both components. Pretreatment with noradrenergic blocking agents (propranolol, phentolamine and phenoxybenzamine) did not diminish the suppressant effect of d-amphetamine, but this effect was reduced by pretreatment with alpha-methyl-para-tyrosine methylester and dopamine blockers (spiroperidol, haloperidol and clozapine) indicating that d-amphetamine was exerting its selective suppressant effect via the release of dopamine. It is suggested that the effects of low doses d-amphetamine on behaviour in conflict situations may provide a useful model for investigating the mode of action of neuroleptic drugs.

Animals↗

Effect of lead exposure on dopaminergic D2 receptor binding in the 21-day-old rat.

The effect of lead on dopaminergic D2 receptor binding, as measured by butaclamol-displaceable [3H]domperidone binding, was studied in the 21-day-old lead-dosed rat. Maternal rats were dosed with 300 ppm and 1000 ppm Pb in drinking water from conception to weaning as previously described [1]. Samples of limbic forebrain and striatum were taken from 21-day-old offspring and assayed for dopamine D2-receptor binding, as outlined by Lazareno and Nahorski [2]. There was a significant (P less than 0.05) decrease in body weight in the animals from which limbic forebrain samples were taken. There were no other significant effects of lead on body- or brain weight. Dopaminergic D2 receptor binding was unaffected by lead administration. These preliminary findings show that dopamine D2 receptor binding is not affected by lead at the doses and exposures used.

Animals↗