Biology subjects

De Luca, M. A.

Publications and source records attributed to De Luca, M. A..

3 recordsLinked to original sources

bioRxiv2025

Long-Term Effects of Adolescent 5F-MDMB-PICA Intravenous self-administration: Neurobehavioral Consequences and medial Prefrontal Cortex Dysfunction in Adult Mice

BackgroundSynthetic Cannabinoids Receptor Agonists (SCRAs) are the largest group of new psychoactive substances monitored worldwide. 5F-MDMB-PICA is a recent SCRA classified as a potent full agonist at CB1/CB2 receptors able to activate the mesolimbic dopamine (DA) transmission in adolescent but not in adult mice. Here, we have studied its reinforcing effects in adolescent mice and characterized the neurochemical and behavioral effects induced in the same animals in adulthood. MethodsWe utilized an intravenous self-administration (IVSA) protocol in adolescent (PND 40-56) CD-1 male mice. In adulthood (PND 66-78), we conducted several behavioral and neurobiological assessments including: Sucrose Preference Test (SPT); Resident Intruder Test (RIT); Olfactory Reactivity Test (ORT); brain microdialysis to quantify DA levels in the medial Prefrontal Cortex (mPFC); and fiber photometry analysis using the GCaMP calcium sensor to monitor excitatory neural dynamics in the mPFC after exposure to an aversive odorant. ResultsWe found that 5F-MDMB-PICA, administered through IVSA in adolescent mice, produced an inverted U-shaped dose-response curve. The dose of 2.5 g/kg/25ul elicited behavior consistent with drug seeking. Adult mice exposed to 5F-MDMB-PICA during adolescence exhibited significant behavioral and neurochemical changes in adulthood compared to control mice. These behaviors included increased aggression, reduced social interaction, an anhedonic state, and an abolishment of mPFC DA response to an aversive odorant, as measured by in vivo brain microdialysis. Moreover, fiber photometry analysis of excitatory neuronal activity in the mPFC showed diminished calcium activity in response to the same aversive odorant in 5F-MDMB-PICA-exposed mice compared to controls. ConclusionsNotably, this study is the first to demonstrate that adolescent mice can acquire and sustain IVSA of 5F-MDMB-PICA. Furthermore, it highlights the long-term behavioral and neurochemical changes associated with adolescent exposure to 5F-MDMB-PICA, underscoring the potential detrimental effects of its use during this critical developmental period.

neuroscience↗

bioRxiv2021

Astrocytic Regulation of Basal Ganglia Dopamine/D2-Dependent Behaviors

Astrocytic involvement in dopamine dynamics related to motivational and sensorimotor gating abilities is unknown. We found that dysbindin-1 (Dys1) hypofunction increases the activity of astrocytes, which express only the isoform Dys1A that is reduced in the caudate of patients with schizophrenia. Astrocytic Dys1A disruption resulted in avolition and sensorimotor gating deficits, increased astrocytic dopamine D2 receptors and decreased dopaminergic tone within basal ganglia. Notably, astrocytic Dys1A hypofunction disrupted dopamine dynamics linked to reward expectancy and interconnected with astrocytes Ca2+ responses mainly in the globus pallidus externus (GPe). Finally, we proved these phenotypes were mediated by D2 receptors in astrocytes as their selective deletion in astrocytes either in GPe or SNc/VTA enhanced motivation and sensorimotor gating abilities as well as dopaminergic release in the GPe. Therefore, astrocytes control motivational and sensorimotor gating processes through Dys1A/D2-dependent mechanisms within the basal ganglia.

neuroscience↗

bioRxiv2017

Brainwide Mapping Of Endogenous Serotonergic Transmission Via Chemogenetic-fMRI

Serotonergic transmission affects behaviours and neuro-physiological functions via the orchestrated recruitment of distributed neural systems. It is however unclear whether serotonins modulatory effect entails a global regulation of brainwide neural activity, or is relayed and encoded by a set of primary functional substrates. Here we combine DREADD-based chemogenetics and mouse fMRI, an approach we term \"chemo-fMRI\", to causally probe the brainwide substrates modulated by phasic serotonergic activity. We describe the generation of a conditional knock-in mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show that chemogenetic stimulation of the serotonin system does not affect global brain activity, but results in region-specific activation of a set of primary target regions encompassing parieto-cortical, hippocampal, and midbrain structures, as well as ventro-striatal components of the mesolimbic reward systems. Many of the activated regions also exhibit increased c-Fos immunostaining upon chemogenetic stimulation in freely-behaving mice, corroborating a neural origin for the observed functional signals. These results identify a set of regional substrates that act as primary functional targets of endogenous serotonergic stimulation, and establish causation between phasic activation of serotonergic neurons and regional fMRI signals. They further highlight a functional cross-talk between serotonin and mesolimbic dopamine systems hence providing a novel framework for understanding serotonin dependent functions and interpreting data obtained from human fMRI studies of serotonin modulating agents.

neuroscience↗