Biomedical subjects

S Prisco

Publications and source records attributed to S Prisco.

4 recordsLinked to original sources

PubMed1995

Differential effects of acute and chronic fluoxetine administration on the spontaneous activity of dopaminergic neurones in the ventral tegmental area.

1. Electrophysiological techniques were used to study the effects of fluoxetine and citalopram on the basal activity of dopaminergic neurones in the ventral tegmental area (VTA) and substantia nigra, pars compacta (SNc) of rats. 2. Acute i.v. injection of fluoxetine (20-1280 micrograms kg-1) caused a dose-dependent inhibition of the firing rate of VTA dopaminergic neurones, but did not affect the activity of dopaminergic cells in the SNc. Citalopram (20-1280 micrograms kg-1, i.v.) inhibited the firing rate of dopaminergic neurones in the VTA, but its effect (maximal inhibition: 14 +/- 7%) was less pronounced than that of fluoxetine (maximal inhibition: 34 +/- 7%). 3. Pretreatment with mesulergine (80 micrograms kg-1, i.v.), a 5-hydroxytryptamine2C/2B (5-HT2C/2B) receptor antagonist, blocked the inhibitory effect of fluoxetine on VTA dopaminergic cells. Selective lesions of 5-hydroxytryptaminergic neurones by the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), abolished the fluoxetine-induced reduction of VTA dopaminergic activity. 4. In a series of experiments, fluoxetine (10 mg kg-1, i.p.) was administered once daily for 21 consecutive days. Acute i.v. administration of fluoxetine (20-1280 micrograms kg-1, 72 h after the last i.p. injection) did not cause any change in the basal firing rate of VTA dopaminergic neurones in treated rats, whereas it induced the typical inhibitory effect in control animals. A group of rats chronically treated with fluoxetine, received i.v. m-chlorophenylpiperazine (mCPP; 10-320 micrograms kg-1), a 5-HT2C/2B receptor agonist. This drug significantly inhibited VTA dopaminergic function in control rats, but did not modify the basal activity of dopaminergic cells in animals given chronic fluoxetine. 5 It is concluded that fluoxetine inhibits dopaminergic function in the VTA by enhancing the synaptic levels of 5-HT, which possibly acts through the 5-HT2C/2B receptor subtype. Repeated treatment with fluoxetine induces tolerance to its inhibitory effect on dopaminergic activity, possibly as a consequence of down-regulation of 5-HT2C/2B receptors. The effects of fluoxetine on VTA dopaminergic cell activity might be relevant for its therapeutic actions and may explain the origin of the reported cases of akathisia.

Animals↗

PubMed1994

Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo.

Electrophysiological techniques were used to study the effects of various serotonin (5-HT) agonists and antagonists on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of rats. Systemic administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.25-80 micrograms/kg i.v.) increased the firing rate of the majority (75%) of DA cells studied and stimulated their bursting activity. A subpopulation (25%) of DA neurons was inhibited by 8-OH-DPAT. Selective lesions of 5-HT neurons by the neurotoxin 5-7-dihydroxytryptamine abolished completely the excitatory effect of 8-OH-DPAT on both firing rate and bursting activity of DA neurons. Microiontophoretic application of 8-OH-DPAT into the VTA did not cause any change in the firing rate of DA neurons. Treatment with the selective 5-HT1B agonist CGS 12066B (7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrolo[1,2-a] quinoxaline 1:2 maleate salt) (1.25-160 micrograms/kg i.v.) did not cause any change in basal firing rate of VTA DA cells. Systemic administration of trifluoromethylphenylpiperazine (TFMPP) (1.25-160 micrograms/kg i.v.) and m-chlorophenylpiperazine (mCPP) (1.25-320 micrograms/kg i.v.), two mixed 5-HT1B/5-HT1C receptor agonists, significantly reduced the firing rate of all VTA DA neurons studied. The effect of mCPP (maximal inhibition, 40%) was more pronounced compared to that of TFMPP (maximal inhibition, 25%). Microiontophoretic application of mCPP into the VTA caused a marked inhibition of the basal activity of DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1993

Tertatolol, a new beta-blocker, is a serotonin (5-hydroxytryptamine1A) receptor antagonist in rat brain.

The interaction of tertatolol (d,l-hydroxy-2'-t-butylamino-3'propyloxy-8-thiochromane HCl) with 5-hydroxytryptamine (serotonin; 5-HT) receptors in several brain areas were investigated. Both ligand binding techniques and an electrophysiological approach were used. First, the affinity of tertatolol for different 5-HT receptor subtypes was measured, as assayed by a competition binding experiment using specific ligands in several brain areas. It was found that (-)-tertatolol binds to 5-HT1 receptor subtypes in rat brain, particularly the 5-HT1A subtype in the hippocampus (Ki = 5.9 nM). (-)-Tertatolol showed much lower affinity for 5-HT1B (Ki = 118.4 nM), 5-HT1C (Ki = 699.6 nM) and 5-HT2 (Ki = 678.6 nM) receptors. The binding of tertatolol to hippocampal 5-HT1A receptors was stereospecific in that the affinity of (+)-tertatolol to these receptors (Ki = 311.6 nM) was about 20 times lower as compared to that of (-)-tertatolol. There was no significant binding of tertatolol to 5-HT1D, 5-HT3, alpha-1 adrenergic receptors or to the serotonin uptake site. Electrophysiological techniques were used to study the effects of (-)-tertatolol on the activity of 5-HT-containing neurons in the rat dorsal raphe nucleus. Acute i.v. injection of (-)-tertatolol caused a slight increase in the basal firing rate of the majority of 5-HT neurons studied. Pretreatment with (-)-tertatolol (1 mg/kg i.v.) significantly reduced the inhibitory effect of 8-hydroxy-2-(di-n-proylamino) tetralin (0.25-64 micrograms/kg i.v.) on the firing rate of dorsal raphe nucleus 5-HT neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Chronic treatment with DAU 6215, a new 5-HT3 receptor antagonist, causes a selective decrease in the number of spontaneously active dopaminergic neurons in the rat ventral tegmental area.

Electrophysiological techniques were used to study the effects of the new compound, DAU 6215 ((3-alpha-tropanyl) 1H-benzimidazolone-3-carboxamide chloride), a selective 5-HT3 receptor antagonist, on the activity of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Acute i.v. injections of DAU 6215 did not cause any change in the basal firing rate of DA neurons in the SNc or in the VTA. Pretreatment with DAU 6215 did not modify the inhibitory effect of apomorphine on the firing rate of midbrain DA neurons. Acute s.c. administration of DAU 6215 caused a significant increase in the number of spontaneously active DA neurons in the VTA but not in the SNc. This effect was similar to that of acute clozapine, whereas acute haloperidol caused a significant increase of spontaneously active DA neurons in both the SNc and the VTA. Repeated consecutive s.c. administration of DAU 6215 and clozapine for 21 days produced a significant decrease in the number of spontaneously active DA neurons in the VTA but not in the SNc. Chronic haloperidol (21 days) decreased the number of DA cells both in the SNc and VTA. The effect of chronic DAU 6215 on the activity of VTA DA neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. These findings indicate that DAU 6215 may have potential antipsychotic activity, probably associated with a low incidence of extrapyramidal side-effects.

Animals↗