clozapine and vanoxerine

It is well known that amphetamine induces disrupted prepulse inhibition (PPI) in humans and rodents. We have previously reported that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA) induces multiple behavioral responses, such as increased locomotor activity and head-twitch response in rodents. To reveal the characteristics of p-OHA on sensorimotor function in rodents, herein we tested the effects of p-OHA on PPI in mice. i.c.v. administration of p-OHA dose-dependently induced PPI disruptions for all prepulse intervals tested. This effect of p-OHA on PPI was attenuated by pretreatment with haloperidol or clozapine. p-OHA-induced PPI disruptions were also attenuated by pretreatment with L-741,626 (a selective D(2) receptor antagonist), L-745,870 (a selective D(4) receptor antagonist) or 6-hydroxydopamine (a neurotoxin which targets DA-containing neurons), but not by SCH 23390 (a selective D(1) receptor antagonist), eticlopride (a D(2)/D(3) receptor antagonist) or GBR 12909 (a DA-reuptake inhibitor). These results indicate that selective blockade of either the D(2) or D(4) receptor subtype may prevent disruption of PPI induced by p-OHA via presynaptic DA release.

Topics: Animals; Benzazepines; Clozapine; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Haloperidol; Indoles; Injections, Intraventricular; Male; Mice; Mice, Inbred Strains; Oxidopamine; p-Hydroxyamphetamine; Piperazines; Piperidines; Pyridines; Pyrroles; Reflex, Startle; Salicylamides; Sensory Gating; Sympathomimetics; Synaptic Transmission

This study compared the interaction between noradrenaline (NA) and dopamine (DA) mechanisms in the prefrontal (PFCX) and in the parietal (ParCX) and occipital (OccCX) cortex. The effect of reboxetine and desipramine, two NA transporter blockers, of mianserin, an antagonist of alpha2 and 5-HT2 receptors, and of clozapine, an atypical antipsychotic, on dialysate DA in the medial PFCX, ParCX and OccCX was studied. We also assessed the influence of a prior 6-hydroxydopamine (6-OHDA) lesion of the dorsal noradrenergic bundle (DNAB) on the effect of reboxetine and clozapine on dialysate DA in the PFCX and ParCX. Systemic administration of reboxetine and desipramine dose-dependently increased dialysate DA in the PFCX but not in the ParCX and OccCX. In contrast, mianserin and clozapine raised dialysate DA in the ParCX and OccCX to an even larger extent than in the PFCX. 6-OHDA lesions of DNAB abolished the increase of dialysate DA elicited by reboxetine in the PFCX and by clozapine both in the PFCX and in the ParCX. It is concluded that, although PFCX and ParCX/OccCX share the presence of a strong control of DA transmission by NA through alpha2 receptors, they differ in the extent to which DA is cleared from the extracellular compartment by uptake through the NA transporter. This process, although extensive in the PFCX, appears insignificant in the ParCX and OccCX, probably as a result of the higher ratio of NA to DA resulting in exclusion of DA from NA transporter.

Topics: Analysis of Variance; Animals; Cerebral Cortex; Clozapine; Desipramine; Dopamine; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Interactions; Extracellular Space; Male; Mianserin; Microdialysis; Morpholines; Neural Pathways; Norepinephrine Plasma Membrane Transport Proteins; Oxidopamine; Piperazines; Rats; Rats, Sprague-Dawley; Reboxetine; Serotonin Antagonists; Symporters; Time Factors

The purpose of the present study was to establish the extent to which dopamine uptake inhibitors, for example, amfonelic acid (AFA) and GBR 12909, differentially affect the haloperidol- and clozapine-induced activation of dopamine neurons. In the striatum and nucleus accumbens, the haloperidol-induced increases in dopamine synthesis and metabolism, as well as striatal dopamine release, were either potentiated or unaffected by AFA or GBR 12909. In contrast, AFA or GBR 12909 markedly attenuated the clozapine-induced increases in dopamine synthesis, metabolism, and release. However, the clozapine-induced increase in dopamine synthesis within tuberoinfundibular dopamine neurons was not significantly altered by AFA treatment. AFA and GBR 12909, appear to differentially affect the haloperidol- and clozapine-induced activation of nigrostriatal and mesocorticolimbic dopamine neurons. However, the inhibitory effect of AFA on the clozapine-induced activation of dopamine neurons does not extent to the stimulatory effect of clozapine on tuberoinfundibular dopamine neurons.

Topics: Animals; Clozapine; Dopamine; Haloperidol; Male; Nalidixic Acid; Naphthyridines; Neurons; Neurotransmitter Uptake Inhibitors; Piperazines; Rats; Rats, Sprague-Dawley

The present study has employed the technique of fast cyclic voltammetry to measure electrically-evoked dopamine release within the central amygdaloid complex in a rat brain slice. Local electrical stimulation caused the release of an electroactive substance which was identified, biochemically and pharmacologically, as being neuronal dopamine. Dopamine release could be inhibited by the dopamine D2 receptor agonist, quinpirole, but not by the D1 receptor agonist, SKF38393. Quinpirole-induced inhibitions were antagonized by sulpiride, metoclopramide and clozapine but not by SCH23390. It is concluded that dopamine release in the amygdala can be modulated by presynaptic D2 receptors which appear to be the same type as those found in striatum and nucleus accumbens.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; Amygdala; Animals; Antipsychotic Agents; Benzazepines; Clozapine; Dopamine; Electric Stimulation; Ergolines; Male; Metoclopramide; Neurotransmitter Uptake Inhibitors; Nialamide; Piperazines; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Secretory Rate; Sulpiride