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Biomedical subjects

L Baran

Publications and source records attributed to L Baran.

At least 73 records · Page 4Linked to original sources

Role of 5-hydroxytryptamine receptor subtypes in the 1-[3-(trifluoromethyl)phenyl] piperazine-induced increase in threshold for maximal electroconvulsions in mice.

The effect of 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), a 5-hydroxytryptamine (5-HT) receptor agonist, on the threshold for maximal electroconvulsions was studied in mice. TFMPP in intraperitoneal (i.p.) doses of 10, 20 and 40 mg/kg increased the convulsive threshold (the amperage necessary to produce the hindleg tonic extensor component of seizures in 50% of animals) by 28, 60, and 85%, respectively. The effect of TFMPP (20 mg/kg) was dose-dependently blocked by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine (NAN-190), prazosin, spiperone, mesulergine, ketanserin, and ritanserin. On the other hand, pindolol and cyanopindolol had no effect on the convulsive threshold increased by TFMPP. The results indicate that the TFMPP-induced decrease in the susceptibility to seizures is connected to stimulation of 5-HT2 or of both 5-HT1C and 5-HT2 receptors. Moreover, alpha 1-adrenoceptors also appear to be engaged in this effect.

Animals↗

Serotonin1B receptor ligands in the nucleus accumbens shell do not affect the discriminative stimulus effects of amphetamine in rats.

Enhanced dopamine neurotransmission particularly, in the target area of the mesolimbic system, i.e. the nucleus accumbens (NAc), seems to be critical for the behavioral effects of amphetamine in rodents. Nonetheless, recent findings have also demonstrated a modulatory role of 5-hydroxytryptamine (5-HT; serotonin) in these effects. In the present study, we examined whether 5-HT1B receptors in the NAc shell are engaged in the discriminative stimulus of amphetamine. To this end male Wistar rats were trained to discriminate amphetamine (1 mg/kg, ip) from saline (ip) in a two-lever, water reinforced fixed ratio (FR) 20 task. After acquiring the amphetamine-saline discrimination, rats were stereotaxically implanted with bilateral cannulae aimed at the NAc shell and then infused with selective 5-HT1B receptor ligands. The ability of these drugs to substitute for or to alter (enhance or antagonize) the discriminative stimulus effects of amphetamine was examined. When given systemically, amphetamine (0.125-1 mg/kg) produced a dose-dependent increase in drug-lever responding. In substitution studies, microinjection of the 5-HT1B receptor agonist CP 93129 (1-10 microg/side) or the 5-HTIB receptor antagonist GR 55562 (1-10 microg/side) into the NAc shell did not evoke amphetamine-lever responding. Combination tests of 5-HT1B receptor ligands demonstrated that local injection with fixed doses of CP 93129 (1 or 10 microg/side) or GR 55562 (1 or 10 microg/side) with the submaximal doses of amphetamine (0.125-0.5 mg/kg) did not modify dose-response curves of the psychostimulant, nor did it affect its ED50 value. Our results seem to exclude a role for the NAc shell 5-HT1B receptors in the control of the discriminative stimulus effects of amphetamine. These findings also show that pharmacological stimulation of those receptors does not affect the amphetamine discrimination in rats.

Amphetamine↗

The anxiolytic-like effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists.

The effect of six 5-HT3 receptor antagonists: ondansetron (0.01-3 mg/kg ip), granisetron (0.01-1 mg/kg ip), zacopride (0.01-3 mg/kg ip), tropisetron (0.001-0.1 mg/kg ip), MDL 72222 (0.01-3 mg/kg ip) and DAU 6215 (0.01-3 mg/kg sc) were examined in the conflict drinking test (Vogel test) and in the elevated plus-maze test in rats. Ondansetron (0.1-0.3 or 1 mg/kg), zacopride (0.1-1 mg/kg) and tropisetron (0.01 mg/kg) increased the punished responding in the Vogel test and showed anxiolytic effects in the elevated plus-maze test. Their effects were limited to a narrow dose range and were not dose-dependent. Granisetron (0.1 mg/kg) exhibited an anti-conflict activity, but was ineffective in the elevated plus-maze test. MDL 72222 and DAU 6215 were ineffective in both those tests. On the other hand, diazepam (2.5-10 mg/kg), used as a reference drug, was active in either procedure and its effects were dose-dependent. These results indicate that an anxiolytic-like activity is not a common characteristic of 5-HT3 receptor antagonists. Moreover, even the anxiolytic action of drugs which were active in the experimental models used should be accepted with caution.

Animals↗

Captopril lacks the antidepressant-like activity in animal models.

Captopril, an angiotensin converting enzyme inhibitor, was evaluated for a potential antidepressive activity in several animal models. The drug administered in doses of 3-30 mg/kg ip neither affected the reserpine- or apomorphine-induced hypothermia in mice nor reduced the immobility time in the forces swimming test in mice and rats. Moreover, captopril administered repeatedly (10 mg/kg ip, twice daily for 14 days) neither changed the density or affinity of cortical beta-adrenoceptors nor modified the nomifensine-induced locomotor hyperactivity in rats. These results suggest that captopril has no antidepressant-like activity in animal models.

Analysis of Variance↗

Repeated treatment with imipramine, amitriptyline or electroconvulsive shock does not affect the 8-OH-DPAT-induced increase in food intake in free feeding rats.

We studied the effect of repeated treatment with imipramine, amitriptyline (10 mg/kg po, twice daily for 14 days) or electroconvulsive shock (ECS, once daily for 10 days) on the 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced increase in food intake in free feeding rats. The response to 8-OH-DPAT, measured 24 h after the last administration of the antidepressant drugs or ECS, was not modified. These results, together with literature data, indicate that the presynaptic 5-HT1A receptors involved in the 8-OH-DPAT-induced feeding are not affected by long-term antidepressant administration.

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

Effect of repeated administration of antidepressant drugs on the isoprenaline-induced drinking in rats.

The effect of acute (single dose) and repeated (twice daily, for 21 days) administration of imipramine, amitriptyline, citalopram, mianserin and rolipram (the latter drug in a dose of 5 mg/kg po, all the other drugs in a dose of 10 mg/kg po) on drinking induced by isoprenaline (50 micrograms intracerebroventricularly (icv), 2 h after the single dose, 2 and 72 h after the last does of the antidepressants) was studied in rats. It was found that repeated, but not acute, treatment with imipramine, amitriptyline and rolipram significantly reduced the response to isoprenaline. The effect of amitriptyline and rolipram was observed 2 and 72 h after their last administration, while that of imipramine only 72 h after its last dose. Citalopram and mianserin were ineffective after both acute and repeated administration.

Amitriptyline↗

The influence of neuroleptics on the behavioural effect of 5-hydroxytryptophan.

The antagonism of neuroleptics of various groups (chlorpromazine, chlorprothixene, clopenthixol, clozapine, flupenthixol, fluphenazine, haloperidol, levomepromazine, mepazine, perazine, perphenazine, pimozide, prochlorperazine, promazine, spiperone, thiopromazine, thioridazine, trifluperazine, trifluperidol, triflupromazine) towards L-5-hydroxytryptophan (5-HTP) was assessed on the basis of inhibition of characteristic head-twitches. ED50 was assayed in mice and rats. The results indicate that all investigated neuroleptics inhibit the action of 5-HTP and their ED50 values are, as a rule, lower than the values of ED50 for catalepsy. That action is for the majority of neuroleptics more pronounced in mice than in rats. The present paper disucsses possible serotonergic, dopaminergic and also noradrenergic mechanism of action of neuroleptics in the 5-HTP test.

5-Hydroxytryptophan↗

The lack of antidepressant properties and a potent central antiserotonin activity of Org 8282.

A potential antidepressant activity and an antiserotonin action of Org 8282, delta (13b, 4a), 4a-carba-mianserin, was studied in mice and rats. Org 8282 did not affect the reserpine-induced hypothermia, hypoactivity and ptosis, did not modify the apomorphine-induced hypothermia and the TRH-induced hyperthermia in mice, did not change the motor stimulation and stereotypy produced by amphetamine. It was inactive in the behavioral despair test in rats and mice. On the other hand, Org 8282 inhibited the head twitch reaction after 5-HTP in mice, the tryptamine-induced clonic convulsions of forepaws in rats, the hyperthermia produced by fenfluramine and m-CPP in rats kept at a high ambient temperature, and the quipazine-induced stimulation of the flexor reflex activity in the spinal rat. These results indicate that Org 8282 is inactive in tests commonly applied for assessment of antidepressant action but--like mianserin--it exerts an antiserotonin activity.

Animals↗