Biology subjects

Ghilotti, M. G.

Publications and source records attributed to Ghilotti, M. G..

3 recordsLinked to original sources

bioRxiv2026

Chronic cocaine exposure negatively impacts Long-COVID-like outcomes produced by the SARS-CoV-2 spike protein in the rat

Acute COVID-19 outcomes are exacerbated by substance use, however, the impact of substance use on Long-COVID is unknown. Here, we investigated the impact of chronic cocaine administration on spike-induced Long-COVID-like outcomes in the rat. Rats received intermittent chronic cocaine administration and a single intravenous injection of the SARS-CoV-2 spike protein. Two months following spike administration, Long-COVID-like outcomes were assessed. Exposure to spike protein in the presence of cocaine produced a persistent reduction in weight gain as compared with controls or spike protein alone. Further, cocaine-treated rats exposed to spike had lower withdrawal thresholds compared to control animals as well as their own baseline, suggesting increased pain sensitivity. Spike and/or cocaine increased the ratio of interleukin-6 (IL-6) to interleukin-10 (IL-10) levels in the hippocampus, indicating a shift towards a proinflammatory state. Paw withdrawal thresholds were positively correlated with IL-10 levels in the hippocampus and prefrontal cortex. Regarding olfaction, rats exposed to spike spent less time sniffing an odor attractant. Cocaine produced an anxiolytic-like phenotype during the elevated plus maze test. Further analysis of behaviors on the maze revealed that the latency to enter the open arms was shorter in rats exposed to spike or cocaine, suggesting a possible impulsive-like phenotype in these animals. These findings demonstrate the negative impact of cocaine on Long-COVID-like outcomes suggesting a need for increased clinical observations of people with co-occurring Long-COVID and cocaine use disorder. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/729575v1_ufig1.gif" ALT="Figure 1"> View larger version (10K): org.highwire.dtl.DTLVardef@12fdc19org.highwire.dtl.DTLVardef@11b1b0dorg.highwire.dtl.DTLVardef@8d1e21org.highwire.dtl.DTLVardef@b53d20_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

The Effects of Ketamine on Methamphetamine Withdrawal-Induced Anxiety and Drug-Seeking Behaviors in the Rat

BackgroundThe use of methamphetamine has continued to rise in the US. In addition to facilitating dopamine neurotransmission, methamphetamine indirectly increases glutamate release which activates N-methyl-D-aspartate receptors (NMDARs). Ketamine is a noncompetitive NMDAR antagonist. Ketamine also has actions on -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and promotes synaptogenesis. Thus, we hypothesized that ketamine may be a potential therapeutic to reduce methamphetamine-seeking behaviors and associated negative affect in a rat model. MethodsMale and female rats underwent methamphetamine or saline intravenous self-administration for 10 sessions, followed by extinction training. Rats received ketamine or saline treatment either prior to 10 daily extinction sessions or only prior to the last extinction session. Anxiety-like behaviors were measured 24 hours after extinction, followed by cue-induced and drug-primed reinstatement two and six days later respectively. ResultsMethamphetamine withdrawal increased anxiety-like behaviors in male rats on the elevated plus maze test compared to rats that self-administered saline. Moreover, anxiety-like behaviors were significantly attenuated by daily ketamine treatment during extinction. Drug-primed but not cue-induced reinstatement, tested six days after the last extinction session, was significantly attenuated in male rats that received ten or one ketamine treatments during extinction compared with rats receiving vehicle during extinction. Ketamine was ineffective in female rats in reducing cue-induced or drug-primed reinstatement. ConclusionsKetamine may confer sex-specific benefits during methamphetamine withdrawal and relapse vulnerability, particularly by reducing anxiety-like behaviors and attenuating drug-primed reinstatement in males. These results support the potential of ketamine as a targeted adjunct therapy during early methamphetamine abstinence in males.

neuroscience↗

bioRxiv2023

The ventral hippocampus and nucleus accumbens as neural substrates for cocaine contextual memory reconsolidation

Drug craving triggered by cues that were once associated with drug intoxication is a major contributor to continued drug-seeking behaviors. Addictive drugs engage molecular pathways of associative learning and memory. Reactivated memories are vulnerable to disruption by interference with the process of reconsolidation, hence targeting reconsolidation could be a strategy to reduce cue-induced drug craving and relapse. Here we examined the circuitry of cocaine contextual memory reconsolidation and explored neuroplasticity following memory reactivation. Mice underwent chemogenetic inhibition of either nucleus accumbens (NA) neurons or the glutamatergic projection neurons from the ventral hippocampus (vHPC) to NA using inhibitory designer receptors exclusively activated by designer drugs (iDREADD). Mice underwent cocaine conditioned place preference followed by reactivation of the cocaine contextual memory. Clozapine-N-oxide (CNO) was administered after memory reactivation to inhibit either NA neurons or the accumbens-projecting vHPC neurons during the reconsolidation period. When retested 3 days later, a significant reduction in the previously established preference for the cocaine context was found in both conditions. FosTRAP2-Ai14 mice were used to identify neurons activated by cocaine memory recall and to evaluate plasticity in NA medium spiny neurons (MSNs) and vHPC pyramidal neurons upon recall of cocaine memories. Results indicate a significant increase in dendritic spine density in NA MSNs activated by cocaine memory recall, particularly of the thin spine type. Sholl analysis indicated longer dendritic length and more branching of NA MSNs after cocaine memory recall than without memory reactivation. vHPC neurons showed increased spine density, with the most robust change in stubby spines. These results implicate a circuit involving glutamatergic projections from the vHPC onto NA neurons which is necessary for the reconsolidation of cocaine memories. Interruption of cocaine memory reconsolidation reduced drug-seeking behavior.

neuroscience↗