- |||||||||| Trintellix (vortioxetine) / Lundbeck, Takeda
Vortioxetine rescues cognitive deficits resulting from prostate cancer treatment via androgen deprivation therapy (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_9365;
Ongoing experiments are currently exploring the mechanism of ADT effects on cognition and the mechanism by which VTX reverses cognitive deficits induced by ADT. These results may inform new treatments for cognitive decline caused by prostate cancer treatment while preserving the tumor-suppressing effect of androgen deprivation therapy.
- |||||||||| clozapine / Generic mfg.
Selective inhibition of oxytocin receptor expressing neurons in anterior cingulate cortex disrupts consoling in male and female prairie voles (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_9240;
Experimental animals received 3mg/kg injections of clozapine-N-oxide (CNO) 30 min prior to partner reunion and behaviors exhibited by the experimental vole towards the partner during the reunion were scored...Chemogenomic inhibition of ACCOxtr cells disrupted distress-induced allogrooming in both male (p > .05) and female (p > .05) voles. Future experiments will utilize Oxtr-Cre voles for visualization and manipulation of ACCOxtr circuits involved in rodent empathy-like behavior.
- |||||||||| lorazepam / Generic mfg., memantine / Generic mfg.
Imaging the changes in cortex-wide human circuit dynamics under pharmacological manipulation of GABA-A and NMDA receptors (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_9185;
For the slope of the aperiodic component, these spatial patterns reflected not the anatomical hierarchy, but the cortical distribution of GABA-A receptor densities, with opposite directions for lorazepam and memantine effects.We conclude that controlled manipulations of specific synaptic receptors alter cortical dynamics along reliable and distinctive large-scale spatial patterns, which are partially explained by synaptic properties. These spatial patterns provide a reference for interpreting the patterns of corresponding changes due to the same manipulation during cognitive tasks or due to cognitive disorders in our ongoing work.
- |||||||||| clozapine / Generic mfg.
Investigating the contribution of the cerebellar dentate nucleus to cognitive and social processing (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8798;
Mice were injected into the DN bilaterally with either a AAV-hSyn-hM3D(Gq)-mCherry excitatory or AAV-hSyn-hM4D(Gi)-mCherry inhibitory DREADD; these receptors can only be activated by the ligand clozapine-N-oxide (CNO)...Moreover, Gq-mediated activation of the DN resulted in increased cFos expression in the dorsal HPC-CA1 subregion, while Gi-mediated inhibition of the DN resulted in a reduction in cFos expression in the same area. These results show that DN activity is necessary for social recognition, and is sufficient to impact HPC firing, highlighting the importance of cerebellar activity for cognitive processing and cognitive relevant circuits.
- |||||||||| clozapine / Generic mfg.
Manipulation of cerebellar nuclei activity modulates cognition, locomotion, and repetitive behaviors in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8788;
Clozapine-N-oxide (CNO; 10 mg/kg), a synthetic DREADD ligand, was administered via drinking water from postnatal day 21-35...Future experiments will examine how CN-VTA activity influences local and long-distance cerebellar connections. These findings suggest potential avenues for exploring novel pathways in neurodevelopmental disorders like ASD.
- |||||||||| desipramine / Generic mfg.
The epigenetic mechanisms of remote memory impairments in the Kabuki syndrome mouse model (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8624;
Importantly, these deficits were ameliorated by desipramine, suggesting a potential therapeutic approach for Kabuki syndrome through the modulation of Utx's epigenetic mechanism...To delve deeper into this matter, we examined the engram cells at the pivotal stage of learning and memory, mapped the brain-wide reconstruction of engrams, and investigated the dynamic changes of histone methylation in contextual fear memory. The findings will shed the light on the mechanisms of the retention of remote memory.
- |||||||||| clozapine / Generic mfg.
Activity dependent perturbation of E-I network connectivity in the hippocampus during development. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8555;
Between postnatal days 5 and 8 (P5-P8), mouse pups received two daily injections of clozapine-N-oxide (CNO) to activate the expressed DREADDs in pyramidal cells to increase or decrease firing rates of same birthdate neurons...In future work, we expand on these results and investigate the bidirectionality of connectivity change. This experimental paradigm offers a way to both manipulate E/I balance and monitor its consequences in the adult, freely moving animal, which may offer insights into neurodevelopmental disorders.
- |||||||||| propranolol / Generic mfg., amisulpride / Generic mfg.
Dopamine blockade blunts an impact of positive mood on reward sensitivity (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8226;
By contrast, an antagonist of noradrenaline had no effect, suggesting the effect of dopamine blockade arises from a blunted impact of mood on reward sensitivity, and not from reduced arousal. Overall, our results shed light on the role of dopamine in mood dynamics and bring us closer to a mechanistic understanding of how dopamine antagonism leads to the clinical phenomenon of affective blunting over time.
- |||||||||| clozapine / Generic mfg.
Astrocytes enable neuronal representations supporting fear memory (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_8066;
Overall, our results shed light on the role of dopamine in mood dynamics and bring us closer to a mechanistic understanding of how dopamine antagonism leads to the clinical phenomenon of affective blunting over time. Furthermore, by manipulating BLA astrocytes chemogenetically
- |||||||||| clozapine / Generic mfg.
Frustrative nonreward: role of outputs from the nucleus accumbens in reward downshift (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7990;
All animals received systemic injections of clozapine N-oxide (CNO) or vehicle during four 32-to-2% sucrose downshift sessions...Preliminary data from unshifted controls show similar suppression after activation of the NAc-to-VP pathway, but not the NAc-to-GPi pathway, suggesting a motor component to the former pathway independent of reward downshift. These experiments are the first to identify specific pathways implicated in the neurobiological processes governing the response to frustrated nonreward.
- |||||||||| methylphenidate tablet / Generic mfg.
Effects of methylphenidate and R-modafinil on impulsive choice decision making in rats. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7973;
The findings suggest that 1) MPH may not offer therapeutic benefits in reducing impulsivity in treating ADHD; 2) R-modafinil, despite its efficacy in treating substance use disorders, appears to increase impulsivity in low-impulsive subjects, suggesting that we should be cautious when using R-modafinil as an off-label "smart drug" drug; and 3) as desipramine, a selective norepinephrine transporter (NET) inhibitor, produced similar effects as MPH and R-modafinil, it is suggested that a NET-related mechanism may underlie the action of MPH and R-modafinil in impulsivity. Further research is needed to test this hypothesis.
- |||||||||| imipramine / Generic mfg., fluoxetine / Generic mfg., haloperidol / Generic mfg.
The sinking platform test: a novel paradigm to measure persistence in animal models (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7896;
Furthermore, a four-week regimen of voluntary wheel running improved persistence in socially isolated mice.Finally, comparing the transcriptomic profiles of the prefrontal cortex between mice with high and low SPT performance revealed significant enrichment of immediate-early genes associated with susceptibility to chronic stress. These findings underscore the potential of the SPT as a valuable tool for investigating the biological mechanisms underlying persistence and for assessing new interventions aimed at enhancing this trait.
- |||||||||| risperidone / Generic mfg.
Early-life risperidone increases locomotor activity later in life: reconsideration of dose and timing (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7891;
These results show that administering risperidone in a more clinically relevant manner early in life still leads to significant behavioral changes later in young adulthood. The increased activity seen in this model could imply that early-life antipsychotic drugs significantly and permanently impact dopaminergic tone.
- |||||||||| morphine sulphate / Generic mfg., clozapine / Generic mfg.
Characterization of ventral tegmental area neuromedin-s expressing neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7775;
We have found that neuromedin S (NMS) gene expression is increased by chronic morphine in VTA DA neurons...To investigate this, we injected Cre-dependent excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) into the VTA of NMS-Cre mice and administered clozapine-n-oxide (CNO) to activate VTA-NMS neurons...Our initial studies indicate that VTA-NMS neurons project to the nucleus accumbens and lateral hypothalamus, but not the prefrontal cortex. Taken together, these studies suggest that VTA-NMS neurons represent a subset of DA neurons, and that VTA-NMS circuitry may represent a novel target for intervention for OUD.
- |||||||||| amphetamine / Generic mfg., escitalopram / Generic mfg.
Effects of escitalopram on amphetamine withdrawal in rats (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7682;
Interestingly, elevated activity was seen beginning about 3 hours following amphetamine + escitalopram treatment, and activity remained elevated for approximately 5-6 hours in a manner that was escitalopram-dose dependent. Our data suggest that acute withdrawal from amphetamine and major depression may share similar mechanisms, and that investigating amphetamine acute withdrawal might provide insight into the mechanistic determinants of depression.
- |||||||||| Vraylar (cariprazine) / Mitsubishi Tanabe, Recordati, Gedeon Richter, AbbVie
Dopamine D3-receptor preferring D3/D2 partial agonists decrease psychostimulant use disorders-like behaviors in rats (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7623;
In CPP/CPA assays, cariprazine and ESG-1-61 induced significant CPA, while ESG-1-60 did not, supporting further evaluation. In conclusion, our study provides robust preclinical evidence supporting the potential efficacy of D3R-preferring D3R/D2R partial agonists in treating PSUD without significant unwanted side effects commonly associated with D2R blockade.
- |||||||||| clozapine / Generic mfg.
Chemogenetic modulation of projections from the ventral pallidum to the nucleus accumbens affects sucrose consumption but not motivation to work for sucrose in female rats. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7568;
This specificity was achieved by injecting inhibitory or excitatory Cre dependent adeno-associated viruses (AAV) in the VP, and retrograde AAV Cre in the AcbSh.Intraperitoneal injections of clozapine-N-oxide (CNO) resulted in no changes in performance in a progressive ratio task where the rats pressed a lever for banana flavored pellets...Interestingly, excitation or inhibition of this pathway modulated sucrose consumption, implicating this circuit in the control of food intake under non-deprived conditions. Taken together, these results suggest that projections from the VP to the AcbSh modulate food consumption but not motivation to work for food.
- |||||||||| fluoxetine / Generic mfg.
Modeling depression in Rats: Chronic corticosterone administration as a tool for antidepressant efficacy assessment (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7388;
We also investigated whether the observed changes could be reversed by the selective serotonin reuptake inhibitor fluoxetine, which demonstrated good efficacy in clinical trials...To our knowledge, this is the first study directly comparing two protocols of corticosterone administration on behavioral and ex vivo readouts. Together with already published data, our study further supports the value of the corticosterone-induced depression model as a valuable tool to investigate the pathogenesis of depression and to test novel treatment candidates.
- |||||||||| clozapine / Generic mfg.
Role of prelimbic-infralimbic medial prefrontal cortex connection in fear extinction and reinstatement in female rats (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7228;
To test efficacy DREADD actuation on retrieval (day 1 of extinction), extinction and reinstatement, animals received clozapine-N-oxide (CNO) (0.5 mg/kg) one hour prior to each extinction session and the reinstatement session...Chemogenetic activation of the intrinsic mPFC circuitry also increased the freezing during the reinstatement session (P=0.048). Taken together, these findings suggest the presence of a PL-IL conection within the mPFC of female rats, and this circuitry seems to play an inhibitory role in fear extiction and facilitates the fear reinstatment.
- |||||||||| methamphetamine / Generic mfg., propranolol / Generic mfg., haloperidol / Generic mfg.
Effects of post-training dopaminergic and beta-adrenergic antagonism on sensitization (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_7027;
Neither immediate post-injection of haloperidol nor propranolol disrupted conditioned hyperactivity but propranolol dose-dependently attenuated sensitization. Taken together, these results indicate that neither dopaminergic nor beta-adrenergic antagonism disrupted memory consolidation and subsequent conditioned hyperactivity whereas post-training antagonism of beta-adrenergic receptors disrupted development of sensitization through non-memory consolidation process(es).
- |||||||||| fluoxetine / Generic mfg.
The role of neuromodulation in the emergence of individuality in nest architecture (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6975;
Pharmacological and genetic manipulations targeting serotonin transmission, including fluoxetine treatment and Tph2 knockout, disrupted nesting style preferences...Using RNA sequencing and in situ hybridization, we found that a decrease of 5HTR1b and 5HTR2a expression in D1+ neurons correlates with a flat nesting style. Our study further aims to dissect the role of neuromodulation within the striatum for the development of inter-individual variations in nesting behavior.
- |||||||||| zolmitriptan / Generic mfg.
Zolmitriptan, a 5-HT1B receptor agonist, attenuates the acquisition of ethanol preference in adolescent female Sprague-Dawley rats (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6949;
Our findings indicate that activating 5-HT1B receptors through administering zolmitriptan reduced the rewarding effects of ethanol in adolescent female rats, providing further evidence of the role of 5-HT1B receptors in modulating the rewarding effects of various drugs of abuse. Future research will examine the preference for zolmitriptan, as evident in the present study, using a wider range of doses in male and female adolescent rats.
- |||||||||| Dopergin (lisuride) / Bayer
Characterizing non-psychedelic psychedelics: phenotypic fingerprinting of lisuride and LSD (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6920;
Combined, these results suggest that although lisuride may not be acting as a traditional psychedelic, it does impact both motor and cognitive function. Further, robust preclinical phenotypic characterization beyond the HTR is important for identifying non-hallucinogenic compounds to move forward for clinical development.
- |||||||||| clozapine / Generic mfg.
Central Amygdala inactivation abolishes frustrative the effect nonreward downshift without affecting alcohol intake in male rat (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6844;
Vehicle or clozapine N-oxide (CNO; 2 mg/kg, ip), used later to activate the inhibitory designer receptor, was administered 30 min before sessions 11-12...CeA inactivation prior to sucrose downshift eliminated the cSNC effect, which was observed in vehicle controls. However, there was no evidence that CeA inactivation affected preference for 4% alcohol over water.These findings identify the hypothesis that CeA activity is critical for cSNC effect, an outcome consistent with the view that the amygdala plays a central role in frustrative nonreward, which may contribute in vulnerability to alcohol use disorder (AUD).
- |||||||||| fluoxetine / Generic mfg.
Sexually dimorphic reponses of stressed flies to antidepressants (MCP Room S401) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6724;
Moreover, fluoxetine treatment was sinergic with stressors in female flies preference for sucrose. Therefore, female flies seem less sensitive to the putative anti-stress effects of fluoxetine compared to males.
- |||||||||| citalopram / Generic mfg.
Effect of maternal SSRI exposure during pregnancy on the gut microbiome of offspring in rats (MCP Room S401) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6721;
We investigated this by giving pregnant Sprague Dawley mothers citalopram, then using next generation shotgun sequencing methods on feces to quantify gut microbiome alterations in male and female offspring, as well as the mothers...We expect that small changes in the gut microbiome of SSRI treated mothers will be amplified in the offspring. We also expect that male and female rats will show sex specific alterations to the gut with males showing a greater level of change compared to controls.
- |||||||||| fluoxetine / Generic mfg.
Altered prefronto-thalamic loop connectivity and PFC dependent cognitive behaviors in response to early-lifechanges in serotonin signaling (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6647;
We also expect that male and female rats will show sex specific alterations to the gut with males showing a greater level of change compared to controls. A critical developmental stage of the mouse PFC occurs during the first two postnatal weeks, during which environmental stressors, including exposure to selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, result in impaired emotional behaviors in adulthood...We are presently assessing global prefronto-thalamic network activity in-vivo after PNFLX-treatment, aiming to unravel the circuit
- |||||||||| clozapine / Generic mfg.
Clozapine abates autoimmunity in a lupus mouse model (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6416;
Taken together, our results indicate that chronic clozapine exposure ameliorates disease markers in a mouse model of lupus, providing evidence that clozapine can abate autoimmunity. Further research is underway to uncover how clozapine interacts with the immune system that leads to this effect and to probe whether clozapine abates autoimmune psychosis.
- |||||||||| clozapine / Generic mfg.
Temporal coordination of female reproductive axis activity by vasoactive intestinal polypeptide (VIP) expressing cells in the suprachiasmatic nucleus in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6398;
Following recovery, mice were injected with clozapine n-oxide (CNO) either in the morning, prior to the LH surge (3Dq experiment), or the afternoon, around the time of the LH surge (4Di experiment)...We confirmed this possibility by localizing afternoon injections of CNO to RFRP-3 cells, which led to comparable decreases in GnRH and Kp cellular activity. These data indicate the importance of SCNVIP neurons in the temporally coordinated disinhibition of RFRP-3 neuronal activity required for stimulation of GnRH and Kp neurons around the time of LH surge.
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