PubMed Health⌕ Search

PubMed · 12225699

Selective serotonin reuptake inhibitors decrease impulsive behavior as measured by an adjusting delay procedure in the pigeon.

Abstract

The inability to delay gratification (reinforcement or reward) is one index of impulsive behavior. In order to measure the willingness of pigeons to delay reinforcement, an adjustable delay schedule was developed that allowed daily approximations of an indifference point between immediate brief access to reinforcer and delayed, longer access to reinforcer. Acute administration of the anxiolytic alprazolam (5 mg/kg) decreased the length of delay tolerated before a larger reinforcement. Likewise, acute administration of the anxiolytic chlordiazepoxide (10 mg/kg) produced a similar, although not significant, effect. Neither acute nor five daily injections of 8-OH-DPAT, a 5-HT(1A) agonist, or WAY100635, a 5-HT(1A) antagonist, affected the length of the delay period. Chronic (17 day), but not acute injections of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (10 mg/kg), citalopram (10 mg/kg) and paroxetine (3 mg/kg) increased the delay period. When given in addition to 1 mg/kg of 8-OH-DPAT, but not 1 mg/kg WAY100635, the effect of fluoxetine was accelerated in that the increase in delay was observed earlier in the treatment. These data support the use of SSRIs to decrease impulsive behavior. Addition of a 5-HT(1A) agonist, but not a 5-HT(1A) antagonist, to the SSRI may hasten the therapeutic activity of the SSRI in treating impulsivity.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mary C Wolff, J David Leander. 2002. Selective serotonin reuptake inhibitors decrease impulsive behavior as measured by an adjusting delay procedure in the pigeon.. https://doi.org/10.1016/s0893-133x(02)00307-x

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Ca2+ responses in Chinese hamster ovary-K1 cells demonstrate an atypical pattern of ligand-induced 5-HT1A receptor activation.

Little experimental evidence has been reported for diverse signaling via 5-hydroxytryptamine (5-HT)1A receptors despite the fact that agonists seem to be more efficacious at dorsal raphe somatodendritic 5-HT1A autoreceptors than at postsynaptic 5-HT1A receptors. The present study investigated Ca2+ responses in Chinese hamster ovary (CHO)-K1 cells expressing a human 5-HT1A receptor by 5-HT, prototypical 5-HT1A agonists, N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-[(5-methyl-6-; methylaminopyridin-2-yl)-methylaminomethyl]-piperidine (F 14679), and especially N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-[(5-methylpyridin-2-yl)-; methylaminomethyl]piperidine (F 13640) as representative ligands of a new chemical class (methylamino-pyridine) that combines both high efficacy and selectivity for 5-HT1A receptors. 5-HT (pEC50 = 6.70 +/- 0.02) induced a pertussis toxin-sensitive, transient high-magnitude Ca2+ response. High-magnitude Ca2+ responses (Emax, percentage versus 5-HT) were also found with F 13640 (107 +/- 4), 5-carboxamidotryptamine (100 +/- 3), and F 14679 (87 +/- 3). In contrast, the prototypical 5-HT1A receptor agonists buspirone, ipsapirone, and 8-(hydroxy-2-(di-n-propylamino)tetralin, and also flesinoxan and eptapirone, were virtually inactive (< or =5). This atypical pattern of 5-HT1A receptor activation contrasts with the broad spectrum of the ligands' partial agonist properties as observed by measuring guanosine 5'-O-(3-[35 S]thio)triphosphate ([35S]GTPgammaS) binding responses with membranes of either CHO-K1 or C6-glial cells stably expressing a human 5-HT1A receptor. Remarkably, differences between ligands that seem small in the [35S]GTPgammaS binding assay translate into huge differences in the magnitude of Ca2+ responses. Therefore, some of these 5-HT1A ligands (i.e., F 13640) may in a selective way induce responses that may be not at all be achieved with other ligands (i.e., buspirone). In conclusion, the pharmacology of 5-HT1A receptor ligands seems to be codetermined by the effector pathway.

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

The effect of natural clinoptilolite on the serotonergic receptors in the brain of mice with mammary carcinoma.

The ex vivo effect of tribomechanically micronized zeolite (MZ) on the binding of 3H-8-OH-DPAT to 5-HT(1A) and 3H-5-HT to 5-HT(1B) receptors was investigated in the brain of nontumorous (control) and mammary carcinoma bearing female mice. During 14 and 28 days mice were fed with standard food, standard food supplemented with 25% of MZ, or standard food supplemented with 25% of non tribomechanically micronized zeolite (non-MZ). A reduced binding of 3H-8-OH-DPAT to 5-HT(1A) receptors in mammary carcinoma bearing mice was found when compared to control mice fed with standard food for 28 days, suggesting a time dependent alteration of 5-HT(1A) receptors in mammary carcinoma. The addition of MZ for 28 days in these mice abolished the decrease in 5-HT(1A) receptors binding, indicating a possible beneficial effect of MZ, at least on 5-HT(1A) receptors in mammary carcinoma bearing mice. The preliminary data show that MZ administered as a food supplement (25%) for 14 days induced a transient decrease in the binding of 3H-5-HT to brain 5-HT(1B) receptors only in control, but not in tumor-bearing mice, that disappeared after 28 days of MZ-supplemented food administration. The mechanism of the indirect action of MZ on the brain serotonergic receptors might be achieved by the alterations in the electrolytes balance, and/or by the regulation of the immune system.

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

Differential modulation of feline defensive rage behavior in the medial hypothalamus by 5-HT1A and 5-HT2 receptors.

Previous studies have established that the expression of defensive rage behavior in the cat is mediated over reciprocal pathways that link the medial hypothalamus and the dorsolateral quadrant of the midbrain periaqueductal gray matter (PAG). The present study was designed to determine the roles played by 5-HT(1A) and 5-HT(2C) receptors in the medial hypothalamus on the expression of defensive rage behavior elicited from electrical stimulation of the PAG. Monopolar stimulating electrodes were placed in the midbrain PAG from which defensive rage behavior could be elicited by electrical stimulation. During the course of this study, defensive rage was determined by measuring the latency of the "hissing" component of this behavior. Cannula-electrodes were implanted into sites within the medial hypothalamus from which defensive rage behavior could also be elicited by electrical stimulation in order that serotonergic compounds could be microinjected into behaviorally identifiable regions of the hypothalamus at a later time. Microinjections of the 5-HT(1A) receptor agonist 8-OHDPAT (0.1, 1.0 and 3.0 nmol) into the medial hypothalamus suppressed PAG-elicited hissing in a dose-dependent manner. Administration of the 5-HT(1A) antagonist p-MPPI (3.0 nmol) blocked the suppressive effects of 8-OHDPAT upon hissing. The suppressive effects of 8-OHDPAT were specific to defensive rage behavior because this drug (3 nmol) facilitated quiet biting attack. Microinjections of the 5-HT(2C) receptor agonist (+/-)-DOI hydrochloride into the medial hypothalamus (0.5, 1.0, and 3.0 nmol) facilitated the occurrence of PAG-elicited hissing in a dose-dependent manner. In turn, these facilitating effects were blocked by pretreatment with the selective 5-HT(2) antagonist, LY-53,857, which was microinjected into the same medial hypothalamic site. The findings of this study provide evidence that activation of 5-HT(1A) and 5-HT(2) receptors within the medial hypothalamus exert differential modulatory effects upon defensive rage behavior elicited from the midbrain PAG of the cat.

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