Effects of selective serotonin and norepinephrine reuptake inhibitors on depressive‐ and impulsive‐like behaviors and on monoamine transmission in experimental temporal lobe epilepsy

Kumar, Udaya; Medel-Matus, Jesús-Servando; Redwine, Hannah M.; Shin, Don; Hensler, Julie G.; Sankar, Raman; Mazarati, Andréy

doi:10.1111/epi.13321

Cited by 38 publications

(40 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Currently, more and more experimental and clinical research demonstrated the bidirectional relation between epilepsy and associated comorbidities [61][62][63]. Patients with epilepsy, especially with disabling epilepsy, clinically demonstrate not only recurrent seizures, cognition deficits and psychiatric symptoms such as depression and psychosis.…”

Section: Overexpression Of Adk and Comorbidities Associated Epilepsymentioning

confidence: 99%

Adenosine Kinase, a Common Pathologic Biomarker for Human Pharmacoresistant Epilepsy

chen¹,

He²,

Li³

2018

Neuropsychiatry

View full text Add to dashboard Cite

Adenosine kinase (ADK) is the chief adenosine removing enzyme in the brain. Experimental research has highlighted that ADK is a diagnostic and a therapeutic marker for epilepsy. Clinical research from patients with pharmacoresistant epilepsy also indicated that maladaptive changes of ADK lead to recurrent seizures in human chronic epilepsy, including Rasmussen encephalitis, focal cortical dysplasia, mesial temporal lobe epilepsy and Sturge-Weber syndrome. In addition, a subpopulation of remaining neurons demonstrated a revertant fetal expression pattern within the lesions are increasing, indicating that the early stage of developmental microenvironment alteration may impair the temporal transient expression pattern of neuronal ADK from fetal to postnatal brains. Increasing levels of ADK expression and adenosine deficiency caused by high levels of ADK played a crucial role in pharmacoresistant epilepsy and epilepsy associated comorbidities. Dysfunction of adenosine system may be a common pathologic hallmark of human pharmacoresistant epilepsy, which suggested the specific targets in the treatment of epilepsy, comorbidities associated with epilepsy in the patients. Future studies will undoubtedly seek to find the novel therapies targeting on ADK and to uncover the mechanism responsible for these future epilepsy therapies.

show abstract

Section: Overexpression Of Adk and Comorbidities Associated Epilepsymentioning

confidence: 99%

Adenosine Kinase, a Common Pathologic Biomarker for Human Pharmacoresistant Epilepsy

chen¹,

He²,

Li³

2018

Neuropsychiatry

View full text Add to dashboard Cite

show abstract

“…Both behaviors are present in normal and depressed animals, but in models of depression, the animals spend longer time immobile, which is interpreted as a hopelessness/despair state. Cumulative time spent immobile was calculated [29, 30]. …”

Section: Methodsmentioning

confidence: 99%

Kindling epileptogenesis and panic-like behavior: Their bidirectional connection and contribution to epilepsy-associated depression

Medel-Matus

Shin

Sankar

et al. 2017

Epilepsy & Behavior

Self Cite

View full text Add to dashboard Cite

Anxiety is one of the most common comorbidities of epilepsy, which has major detrimental effects on the quality of life. Generalized anxiety disorder (GAD) associated with epilepsy has been receiving most attention. However, several other forms of anxiety reportedly present in epilepsy patients, including panic disorder (PD). In this study, using an animal model of limbic epilepsy, we examined the interplay between epilepsy and panic-like behavior (PLB). Further, considering the high degree of comorbidity between depression on the one hand, and both epilepsy and PD on the other hand, we studied whether and how the presence of PLB in animals with epilepsy would affect their performance in depression-relevant tests. Fifty-day-old male Wistar rats were subjected to repeated alternating electrical stimulations of the basolateral amygdala (BLA) to induce kindling of limbic seizures, and the dorsal periaqueductal gray (DPAG) to induce panic-like episodes. Seizure susceptibility and panic reaction threshold were examined before the first and 24 hours after the last stimulation. At the end of the stimulations, the rats were examined in depression-relevant tests: saccharin preference test (SPT) for anhedonia and forced swimming test (FST) for despair/hopelessness. With regard to kindling, BLA+DPAG stimulation induced more profound increase of seizure susceptibility than BLA stimulation alone (evident as the reduction of the afterdischarge threshold and the increase of the afterdischarge duration). With regard to PLB, the BLA+DPAG stimulation exacerbated the severity of panic-like episodes, as compared with the DPAG stimulation alone. BLA stimulation alone had no effects on panic-like reactions, and DPAG stimulation alone did not modify kindling epileptogenesis. Combined stimulation of BLA and DPAG induced depressive-like behavioral impairments. This is the first experimental study showing bidirectional, mutually exacerbating effect of epilepsy and PLB, and the precipitation of depressive-like state by the epilepsy-PLB comorbidity.

show abstract

“…In order to alleviate the severity of SE and to decrease the frequency of subsequent spontaneous seizures, rats received i.p. injections of diazepam (10 mg/kg) and phenytoin (50 mg/kg) one and four hours after the SE onset (Kumar et al, 2016; Mazarati et al, 2008; Pineda et al, 2014; Pineda et al, 2012). In control animals, saline was injected instead of pilocarpine.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

“…FST was used to examine depressive- and impulsive-like behaviors as described by our group (Kumar et al, 2016; Mazarati et al, 2008; Pineda et al, 2014). The first FST (FST 1 ) was performed 4 weeks after SE; the second (FST 2 ) was conducted during the administration of GalR ligands; some animals underwent the third test (FST 3 ) after the drug washout (Fig.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

“…In a series of studies, we showed that sub-populations of rats with post-status epilepticus (SE) chronic epilepsy consistently presented with either depressive-like, ADHD-like behavioral impairments, or with both (Kumar et al, 2016; Mazarati et al, 2008; Pineda et al, 2014; Pineda et al, 2012). We established that depressive-like behavior stemmed from the suppressed serotonergic transmission in the raphe nucleus (RN) – prefrontal cortex (PFC) pathway.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Galanin contributes to monoaminergic dysfunction and to dependent neurobehavioral comorbidities of epilepsy

Medel-Matus

Shin

Sankar

et al. 2017

Experimental Neurology

Self Cite

View full text Add to dashboard Cite

Status epilepticus (SE) in rats, along with chronic epilepsy, leads to the development of behavioral impairments resembling depressive disorder and/or attention deficit/hyperactivity disorder (ADHD), thus reflecting respective comorbidities in epilepsy patients. Suppressed neurotransmitter tone in the raphe nucleus (RN)-prefrontal cortex (PFC) serotonergic pathway and in the locus coeruleus (LC)-PFC noradrenergic pathway underlies depressive- and impulsive- like behavioral deficits respectively. We examined possible mechanisms leading to the monoamine dysfunction in brainstem efferents, namely modulatory effects of the neuropeptide galanin on serotonin (5-HT) and norepinephrine (NE) signaling. SE was induced in young adult male Wistar rats by LiCl and pilocarpine. Epileptic rats were categorized vis-à-vis behavioral deficits as not impaired, “depressed” and “impulsive”. Depressive- and impulsive- like behaviors were examined in the forced swimming test (FST). The strength of serotonergic transmission in RN-PFC and of noradrenergic transmission in LC-PFC was analyzed using in vivo fast scan cyclic voltammetry. Galanin receptor type 1 (GalR1) / type 2 (GalR2) antagonist M40, and a preferential GalR2 antagonist M871 were administered over 3 days locally into either RN or LC by means of ALZET osmotic minipumps connected to locally implanted infusion cannulas. Intra-RN injection of M40 improved serotonergic tone and depressive-like behavior in epileptic “depressed” rats. Intra-LC injection of M40 improved noradrenergic tone and impulsive-like behavior in epileptic “impulsive” rats. The effects of M40 were only observed in impaired subjects. The treatment did not modify neurotransmission and behavior in naïve and epileptic not impaired rats; in “depressed” rats the effects were limited to serotonergic transmission and immobility, while in “impulsive” rats – to noradrenergic transmission and struggling behavior. Intra-RN administration of M871 exacerbated depressive-like behavior, but had no effects on any other of the examined parameters in any category of animals. These findings suggest that endogenous galanin, acting through GalR1 may be involved in the pathophysiology of epilepsy-associated depression and ADHD via inhibiting RN-PFC serotonergic and LC-PFC noradrenergic transmissions respectively.

show abstract

Effects of selective serotonin and norepinephrine reuptake inhibitors on depressive‐ and impulsive‐like behaviors and on monoamine transmission in experimental temporal lobe epilepsy

Cited by 38 publications

References 37 publications

Adenosine Kinase, a Common Pathologic Biomarker for Human Pharmacoresistant Epilepsy

Adenosine Kinase, a Common Pathologic Biomarker for Human Pharmacoresistant Epilepsy

Kindling epileptogenesis and panic-like behavior: Their bidirectional connection and contribution to epilepsy-associated depression

Galanin contributes to monoaminergic dysfunction and to dependent neurobehavioral comorbidities of epilepsy

Contact Info

Product

Resources

About