Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine

Chen, Zhuo; Tetzlaff, Julie E.; Sripathirathan, Kumar; Carrasco, Gonzalo; Shankaran, Mahalakshmi; Kar, Louis D. Van de; Muma, Nancy A.; Battaglia, George

doi:10.1007/s00213-005-2249-8

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Now it has become also commercially available and been found to be useful tool for experiments with membrane preparations as well as in brain sections [9,10]. Wide application has been found for 11 C and 18 F derivatives of WAY100635 in the in vivo studies [11,12].…”

Section: H][n-[2-[4-(2-[o-methyl-3 H]methoxyphenyl)-1-piperazinyl]ethmentioning

confidence: 97%

Characteristics of Binding of [3H]WAY100635 to Rat Hippocampal Membranes

Parkel

Rinken

2006

Neurochem Res

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Kinetic analysis of binding of [(3)H][N-[2-[4-(2-[O-methyl-(3)H]methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane carboxamide ([(3)H]WAY100635) to 5-HT(1A) receptors in rat hippocampal membranes has revealed complex regulation mechanism for this radioligand. Saturation binding experiments revealed that [(3)H]WAY100635 binds to a single class of receptors with very high apparent affinity (K (D) = 87 +/- 4 pM, B (max) = 15.1 +/- 0.2 fmol/mg protein). The binding was almost irreversible, as the dissociation rate constant obtained k (off) = (7.8 +/- 1.1) x 10(-3) min(-1), means that equilibrium with this radioligand cannot be achieved before 7.5 h incubation at 25 degrees C. Systematic association kinetic studies of [(3)H]WAY100635 binding revealed sharp reaction acceleration at higher radioligand concentration, proposing mechanism of positive cooperativity. The affinities of antagonists determined from competition with [(3)H]WAY100635 did not coincide with their abilities to inhibit 5-HT-dependent activation of [(35)S]GTPgammaS binding probably due to the ligand's kinetic peculiarities. Thus, [(3)H]WAY100635 appears to be an excellent tool for determining receptor binding sites, but its applicability in equilibrium studies is strongly limited.

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Section: H][n-[2-[4-(2-[o-methyl-3 H]methoxyphenyl)-1-piperazinyl]ethmentioning

confidence: 97%

Characteristics of Binding of [3H]WAY100635 to Rat Hippocampal Membranes

Parkel

Rinken

2006

Neurochem Res

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“…Compounds that reverse changes in 5‐HT 1A receptor sensitivity and expression in drug addicts may be useful as a therapy for drug addiction (Akbari, Whitaker‐azmitia & Azmitia 1994; Johns et al . 2002; Chen et al . 2005), but the available findings regarding repeated cocaine treatments in animals do not present a very clear picture.…”

Section: ‐Ht Receptors and Repeated Exposure To Cocainementioning

confidence: 99%

REVIEW: Behavioral evidence for the significance of serotoninergic (5‐HT) receptors in cocaine addiction

et al. 2010

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Cocaine addiction has somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Presently, there is no medication approved for the treatment of cocaine addiction. In recent years, data from the literature (pre-clinical studies and clinical trials) have provided several lines of evidence that serotonin (5-HT) and 5-HT receptors play a modulatory role in the mechanisms of action of cocaine. Here we review the contribution of 5-HT receptor subtypes to cocaine sensitization, discrimination, conditioned place preference, self-administration, reinstatement of seeking behavior and withdrawal symptoms in laboratory animals. Additionally, the consequences of chronic cocaine exposure on particular 5-HT receptor-assigned functions in pre-clinical studies are presented.

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“…Unlike adolescents, adults show no change in 5-HT 1A -stimulated release of any hypothalamic hormone, and also have normal basal hormone levels [85]. Chronic paroxetine administration desensitizes 5-HT 1A receptors [99] and PC exposure (GD 13-20; 30 mg/kg/day) decreases 5-HT 1A -stimulated ACTH release following a 2 week paroxetine treatment period in adult male but not female rats, indicating a differential, sex-specific sensitivity to alterations in serotonergic signaling following PC exposure [100]. PC exposure (GD 1-20; 30 mg/kg/day) alters brain 5-HT 1A expression in a sex-specific manner (Figs.…”

Section: Serotonergic Signaling Throughout Developmentmentioning

confidence: 99%

“…Future studies should investigate functional changes in 5-HT 1A receptors in different brain regions following longer PC exposure paradigms, since it is currently unclear whether earlier exposure will cause similar sex-specific effects on 5-HT 1A function. Since PC exposure does not appear to impact the ability of these receptors to promote release of oxytocin, prolactin, or corticosterone at any age in either sex [100], these results suggest a sensitivity of CRF releasing neurons to PC exposure, in contrast to other neuroendocrine cells of the hypothalamus. Although 5-HT may also be having a direct stimulatory effect on pituitary cells, the interactive roles of CRF and 5-HT in releasing ACTH remains unclear [104,105].…”

Section: Serotonergic Signaling Throughout Developmentmentioning

confidence: 99%

Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors:Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

Williams

Lauder²,

Johns³

2011

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Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine’s effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure.

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Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine

Cited by 5 publications

References 31 publications

Characteristics of Binding of [3H]WAY100635 to Rat Hippocampal Membranes

Characteristics of Binding of [3H]WAY100635 to Rat Hippocampal Membranes

REVIEW: Behavioral evidence for the significance of serotoninergic (5‐HT) receptors in cocaine addiction

Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors:Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

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