Sex differences in the antidepressant-like response and molecular events induced by the imidazoline-2 receptor agonist CR4056 in rats

Hernández-Hernández, Elena; Ledesma-Corvi, Sandra; Yáñez-Gómez, Fernando; Garau, Celia; Gálvez-Melero, Laura; Bagán, Andrea; Escolano, Carmen; García-Fuster, M. Julia

doi:10.1016/j.pbb.2023.173527

Cited by 3 publications

(1 citation statement)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, to what was observed for adolescent rats, the rates of immobility increased in the ECS groups as measured 7 days post-treatment. In conjunction, these data align with the differences in response to certain antidepressants' efficacy previously reported for males and females [ 21 , 32 , 45 – 47 ], as well as with prior data reporting that antidepressants differ in efficacy depending on the age of exposure, being adolescence a less responsive period than adulthood (e.g., [ 21 , 35 , 43 ]). The lack of a beneficial effect in adolescence could be attributed to an excessive ECS intensity for such young animals, which might be causing the observed negative effects, in line with previous studies reporting that the electrical charge for effective responses in young females should be lower than the one used for older animals [ 15 – 20 ].…”

Section: Discussionsupporting

confidence: 88%

Comparing the antidepressant-like effects of electroconvulsive seizures in adolescent and adult female rats: an intensity dose–response study

Ledesma-Corvi,

García-Fuster

2023

Biol Sex Differ

Self Cite

View full text Add to dashboard Cite

Background The induction of electroconvulsive seizures (ECS) in rodents induces sex- and age-specific disparities in antidepressant-like responses, with females and young age being the most unresponsive ones. Since the electrical charge needed to induce an effective convulsion is also altered by these variables, our aim was to compare different dose-intensities of ECS exclusively in female rats, since there is a lack of preclinical data characterizing this particular sex, while also evaluating efficacy during distinctive age periods of treatment (adolescence vs. adulthood). Methods Adolescent and adult female Sprague–Dawley rats were exposed to an intensity dose–response study (55, 75 or 95 mA; 0.6 s, 100 Hz, 1 session/day, 5 days). The particular characteristics of the induced convulsions (tonic, clonic, recovery times) were monitored during treatment. Antidepressant-like responses were evaluated under the stress of the forced-swim test 1-, 3-, and 7-days post-treatment (i.e., improved immobility time as an indicative of an antidepressant-like response), and brains were collected 24 h later (8 days post-treatment) to evaluate potential changes in hippocampal neurogenesis (Ki-67 and NeuroD) by immunohistochemistry. Results The lowest intensities tested of ECS (55 and 75 mA) induced an antidepressant-like effect in adult female rats, but rendered insufficient in adolescence. The lack of efficacy observed in adolescent rats paralleled differences in the characteristics of the seizures induced by ECS as compared to adulthood. In line with prior results, different dose-intensities of ECS modulated hippocampal neurogenesis in a comparable fashion with age (i.e., increased survival of neural progenitors 8 days post-treatment). Conclusions In conjunction, these results reinforce the importance of fine-tuning the parameters of ECS that might render efficacious while considering sex and age as essential variables for treatment response, and suggest that other molecular mechanisms, beside the partial role of hippocampal neurogenesis, might be participating in the antidepressant-like effects induced by ECS.

show abstract

Section: Discussionsupporting

confidence: 88%

Comparing the antidepressant-like effects of electroconvulsive seizures in adolescent and adult female rats: an intensity dose–response study

Ledesma-Corvi,

García-Fuster

2023

Biol Sex Differ

Self Cite

View full text Add to dashboard Cite

show abstract

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Garcia-Fuster,

Colom-Rocha,

Bis-Humbert

2024

Preprint

View full text Add to dashboard Cite

Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood during withdrawal and induced by adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects. We performed 3 independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29–38) with ethanol, cocaine, their combination or vehicle. Following prolonged forced-withdrawal, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood. The results proved no signs of increased negative affect during withdrawal in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated during forced-withdrawal with cannabidiol (and/or ketamine, but just for females) reduced ethanol voluntary consumption in adulthood. Our data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats.

show abstract

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Colom-Rocha,

Bis-Humbert,

García-Fuster

2024

Front. Pharmacol.

View full text Add to dashboard Cite

BackgroundFew studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects.MethodsWe performed three independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29–38) with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Later on, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood.ResultsNo signs of increased negative affect were observed in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated in adulthood with cannabidiol (and/or ketamine, but just for females) reduced their ethanol voluntary consumption.ConclusionOur data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats

show abstract

Sex differences in the antidepressant-like response and molecular events induced by the imidazoline-2 receptor agonist CR4056 in rats

Cited by 3 publications

References 64 publications

Comparing the antidepressant-like effects of electroconvulsive seizures in adolescent and adult female rats: an intensity dose–response study

Comparing the antidepressant-like effects of electroconvulsive seizures in adolescent and adult female rats: an intensity dose–response study

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Contact Info

Product

Resources

About