Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

Samardžić, Janko; Puškaš, Laslo; Obradović, Miljana; Lazić-Puškaš, Dijana

doi:10.2478/acve-2014-0006

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Our results confi rm the statement that in rats during postnatal development there was an overall decrease in BCSFB exchange with increasing age [28]. In a ll studies of rat's CP development different postnatal growth patterns must be considered, because its growth in the third ventricle ended by the 5th postnatal week, but in the fourth and possibly in the lateral ventricles CP extended to develop through the period from P3 to P25 [29][30][31][32][33].…”

Section: Discussionsupporting

confidence: 75%

A morphometric analysis of the postanatal development of the choroid plexus epithelium in the male and female rat

et al. 2014

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Morphometric parameters of the lateral ventricle choroid plexus epithelial cells (average area, perimeter, bounding rectangle area, average nuclear area, nuclear perimeter, nuclear circularity and average nucleocytoplasmic ratio) were studied in postnatal and juvenile (10 th , 16 th and 38 th postnatal days) 15 male and 15 female rats. The results were statistically analyzed by factorial ANOVA.Mean values of epithelial cells area, bounding rectangle area and perimeter were signifi cantly higher in 16 days old, than in 10 and 38 days old rats. Opposite to this, the nucleocytoplasmic ratio was lower in the 16 days old, than in 10 and 38 days old rats. Average nuclear area and perimeter showed similar trends, while nuclear circularity increased from the 10 th to the 38 th day. Signifi cant sex differences were in the epithelial cells area, bounding rectangle area and perimeter, being higher in males than in females in both 16 and 38 days groups. Nucleocytoplasmic ratio was higher in 10 days old male rats, but lower in 16 and 38 days old male rats. Generally, choroid epithelial cells size increased on the 16 th and then decreased on the 38 th day, but still remained higher compared to the 10 th day. Nuclear size after increasing on day 16, also decreased on day 38, but to values lower than on day 10. The general decrease of nucleocytoplasmic ratio which accompanied these changes indirectly suggests a functional decrease. In the investigated period the male rat choroid epithelial cells were larger, but their nucleocytoplasmic ratio, which suggests the functional status, was lower than in females, indicating sex differences in the growth dynamics of the rat choroid plexus.

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Section: Discussionsupporting

confidence: 75%

A morphometric analysis of the postanatal development of the choroid plexus epithelium in the male and female rat

et al. 2014

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“…It is noteworthy to mention that additional kinetic investigation of SH-I-048A could possibly indicate the presence of very low residual concentrations of the compound in brain tissue 72h after dosing, as demonstrated for other benzodiazepine-like compounds after application of similar doses. If that would be the case, the importance of choosing a ligand with a suitable subunit activity profi le, as well as the right time and dosage regimen for its application, becomes even more signifi cant in light of the fi ne tuning of neural plasticity related to the post-injury period and recovery [28,29].…”

Section: Discussionmentioning

confidence: 99%

Delayed Behavioral Effects of SH–I–048A, a Novel Nonselective Positive Modulator of Gabaa Receptors, After Peripheral Nerve Injury in Rats

et al. 2014

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The complex clinical picture of mono-neuropathy following injury of peripheral nerve is often accompanied by changes in the patients' affective states. It has been shown that positive allosteric modulators of GABA A receptors can decrease nociceptive transmission in animal pain models. However, recent fi ndings suggest a possibility that at least some of the antinociceptive effects of benzodiazepines, related to neuropathic painful stimuli, may to a signifi cant degree be a consequence of their anxiolytic action. In this study we evaluated the possible delayed effects of SH-I-048A, a newlysynthesized high-effi cacy nonselective positive modulator of GABA A receptors, on anxiety-like behavior and locomotor activity in Wistar rats with a previously induced peripheral nerve injury. Assessment of behavioral parameters, using spontaneous locomotor activity and elevated plus maze tests, was performed 48h after completion of single-day threei.p. injections treatment consisting of zero, one, two or three doses of SH-I-048А (10 mg/kg). In general, rats' behavior observed 72 h after a moderate peripheral nerve injury did not indicate the persistence of sequelae of mono-neuropathic pain. The rats treated with three doses of SH-I-048А displayed an enhanced immobility time in the locomotor activity test, without concomitant decrease of the total distance traveled. On the other hand, in the group treated with two doses of SH-I-048А, a decrease in the emotional reactivity in the elevated plus maze test was observed. Subtle changes in the regimen of dosing of SH-I-048А affect locomotor activity and anxiety-related behavior in animals with peripheral nerve injury.

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“…Rats were tested at either 30 minutes or 1 week following a single administration of L-655,708 (3 mg/kg, i.p.). The dose was chosen based on a previous study ( Samardzic et al, 2014 ). A time sampling technique was utilized where the most prominent behavior (immobility, swimming or climbing) observed in each 5-second bin was recorded for the first 5 minutes of the test ( Cryan et al, 2005 ).…”

Section: Methodsmentioning

confidence: 99%

Selective Pharmacological Augmentation of Hippocampal Activity Produces a Sustained Antidepressant-Like Response without Abuse-Related or Psychotomimetic Effects

Carreño

Collins

Frazer

et al. 2017

International Journal of Neuropsychopharmacology

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Background:Selective augmentation of hippocampal activity in ways similar to that caused by ketamine may have therapeutic advantages over ketamine, which has psychotomimetic and reinforcing effects likely due to effects outside the hippocampus (i.e., off-target effects).Methods:Here we evaluated the antidepressant-like response to a negative allosteric modulator of α5 subunit- containing gamma aminobutyric acid subtype A receptors, L-655,708, as these receptors are expressed to a much greater extent in the hippocampus than in other brain areas.Results:Systemic administration of L-655,708 produced a sustained antidepressant-like effect in the forced swim test that was comparable with that of ketamine and was blocked by hippocampal inactivation with lidocaine. However, in contrast to ketamine, L-655,708 did not affect prepulse inhibition of startle, nor did it maintain responding in rats trained to self-administer i.v. ketamine.Conclusion:Taken together, these findings suggest that activation of the hippocampus by L-655,708 produces an antidepressant-like effect in the absence of any psychotomimetic or abuse-related effects.

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Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

Cited by 9 publications

References 35 publications

A morphometric analysis of the postanatal development of the choroid plexus epithelium in the male and female rat

A morphometric analysis of the postanatal development of the choroid plexus epithelium in the male and female rat

Delayed Behavioral Effects of SH–I–048A, a Novel Nonselective Positive Modulator of Gabaa Receptors, After Peripheral Nerve Injury in Rats

Selective Pharmacological Augmentation of Hippocampal Activity Produces a Sustained Antidepressant-Like Response without Abuse-Related or Psychotomimetic Effects

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