Effects of 5-HT receptor antagpnist on seizure susceptibility and locomotor activity in DBA/2 mice

Семенова, Т. А.; Ticku, Maharaj K.

doi:10.1016/0006-8993(92)91580-8

Cited by 30 publications

(23 citation statements)

References 16 publications

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“…These data indicate a hyperresponsiveness to two very different stimuli: cocaine and the presentation of a new environment to explore. Others have noted a reduction in exploratory locomotion with a general central serotonergic lesion (Lipska et al, 1992) or by 5-HT3 or 5-HT4 receptor blockade (Semenova and Ticku, 1992). Differences with this current study may be the result of specificity of the serotonergic DR lesions used in this report, which is not seen with systemic pharmacological treatments or following global lesions of all central serotonergic systems.…”

Section: Role Of 57-dht Lesions In Basal and Cocaine-induced Locomotmentioning

confidence: 67%

Serotonergic lesions alter cocaine-induced locomotor behavior and stress-activation of the mesocorticolimbic dopamine system

Morrow

Roth

1996

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Section: Role Of 57-dht Lesions In Basal and Cocaine-induced Locomotmentioning

confidence: 67%

Serotonergic lesions alter cocaine-induced locomotor behavior and stress-activation of the mesocorticolimbic dopamine system

Morrow

Roth

1996

Synapse

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“…The MPDZ protein is thought to affect neuronal excitability by altering the rate or fidelity of signal transduction mediated by a protein(s) with which it interacts, similar to other members of the PDZ domain protein family (Tsunoda et al, 1997;Fanning & Anderson, 1999;Sheng and Sala, 2001). Plausible mechanisms involve MPDZ's interaction with 5-HT 2C and/or GABA B receptors (Ullmer et al, 1998;Becamel et al, 2001;Balasubramanian et al, 2007), both of which influence neuronal excitability and are important therapeutic targets for epilepsy as well as alcohol and drug abuse (Prather et al, 1991;Semenova and Ticku 1992;Lal et al, 1993;Rezazadeh et al, 1993;Bettler et al, 1998;Gatch et al, 2000;Bowery, 2006).…”

Section: Introductionmentioning

confidence: 99%

5-HT2C and GABAB receptors influence handling-induced convulsion severity in chromosome 4 congenic and DBA/2J background strain mice

et al. 2008

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Progress towards elucidating the underlying genetic variation for susceptibility to complex central nervous system (CNS) hyperexcitability states has just begun. Genetic mapping analyses suggest that a gene(s) on mid-chromosome 4 has pleiotropic effects on multiple CNS hyperexcitability states in mice, including alcohol and barbiturate withdrawal and convulsions elicited by chemical and audiogenic stimuli. We recently identified Mpdz within this chromosomal region as a gene that influences alcohol and barbiturate withdrawal convulsions. Mpdz encodes the multi-PDZ domain protein (MPDZ). Currently, there is limited information available about the mechanism by which MPDZ influences drug withdrawal and/or other CNS hyperexcitability states, but may involve its interaction with 5-HT 2C and/or GABA B receptors. One of the most useful tools we have developed thus far is a congenic strain that possesses a segment of chromosome 4 from the C57BL/6J (donor) mouse strain superimposed on a genetic background that is >99% from the DBA/2J strain. The introduced segment spans the Mpdz gene. Here, we demonstrate that handling-induced convulsions are less severe in congenic vs. background strain mice in response to either a 5-HT 2C receptor antagonist (SB242084) or a GABA B receptor agonist (baclofen), but not a GABA A receptor channel blocker (pentylenetetrazol). These data suggest that allelic variation in Mpdz, or a linked gene, influences SB242084-and baclofen-enhanced convulsions. Our results are consistent with the hypothesis that Mpdz's effects on CNS hyperexcitability, including alcohol and barbiturate withdrawal, involve MPDZ interaction with 5-HT 2C and/or GABA B receptors. However, additional genes reside within the congenic interval and may also influence CNS hyperexcitability.

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“…Cyproheptadine therefore either 1) does not decrease motoneuron excitability in neonatal mice, 2) was not at a concentration high enough to produce an effect, or 3) decreased excitability but did not affect disease progression. We believe options 1 and 2 are unlikely because cyproheptadine has previously been shown to block the effects of 5-HT application on neonatal rat motoneurons in vitro (Wang and Dun 1990), and the doses for this study were chosen based on their ability to inhibit 5-HTmodulated effects in vivo (Kilic et al 2011;Semenova and Ticku 1992;Singh and Goel 2010;Yi et al 2011). We therefore believe that these cyproheptadine doses were sufficient to inhibit motoneuron excitability.…”

Section: Discussionmentioning

confidence: 99%

“…Each pup in the litter was given the same drug dose, and care was taken to minimize the disruption of the litter. These cyproheptadine concentrations were chosen because of their clinical relevance (Kilic et al 2011;Semenova and Ticku 1992;Singh and Goel 2010;Yi et al 2011).…”

Section: Drug Administrationmentioning

confidence: 99%

Effect of fluoxetine on disease progression in a mouse model of ALS

Koschnitzky

Quinlan

Lukas

et al. 2014

Journal of Neurophysiology

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Koschnitzky JE, Quinlan KA, Lukas TJ, Kajtaz E, Kocevar EJ, Mayers WF, Siddique T, Heckman CJ. Effect of fluoxetine on disease progression in a mouse model of ALS. J Neurophysiol 111: 2164-2176, 2014. First published March 5, 2014 doi:10.1152/jn.00425.2013.-Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5-11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1 G93A and control: nontransgenic and SOD1 WT ) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1 G93A mice reached end stage ϳ8 days (ϳ6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models. amyotrophic lateral sclerosis; motoneuron excitability; fluoxetine; Prozac; antidepressant

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Effects of 5-HT receptor antagpnist on seizure susceptibility and locomotor activity in DBA/2 mice

Cited by 30 publications

References 16 publications

Serotonergic lesions alter cocaine-induced locomotor behavior and stress-activation of the mesocorticolimbic dopamine system

Serotonergic lesions alter cocaine-induced locomotor behavior and stress-activation of the mesocorticolimbic dopamine system

5-HT2C and GABAB receptors influence handling-induced convulsion severity in chromosome 4 congenic and DBA/2J background strain mice

Effect of fluoxetine on disease progression in a mouse model of ALS

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