Biology subjects

Joshi, D. D.

Publications and source records attributed to Joshi, D. D..

3 recordsLinked to original sources

bioRxiv2026

Serial, as opposed to parallel, insular-prefrontal cortex processing determines the tendency to make risky decisions

Adaptive decision-making under ambiguity requires constant integration of reward- and loss-related information to guide behaviour. In humans and rodents, not all individuals maximise gains in decision-making tasks, such as the Iowa Gambling task or its rodent version, the Rat Gambling task (rGT). While the prefrontal and insular cortices have each been shown independently to support optimal probabilistic decision-making, how they interact functionally to shape individual differences in performance remains unclear. Here, we investigated the consequences of bilateral baclofen/muscimol-mediated inactivation of the prelimbic cortex (PLC) or the anterior insular cortex (AIC) vs. their functional disconnection on the performance of Sprague Dawley rats identified as safe (SDMs) or risky decision makers (RDMs) in the RGT. AIC inhibition decreased advantageous choice in SDMs, whereas it increased win-stay responding in RDMs. In contrast, PLC inhibition primarily affected lose-shift behaviour, reducing sensitivity to losses in SDMs while enhancing adaptive switching in RDMs. Functionally disconnecting the PLC from the AIC, which had no effect on the performance of SDMs, improved decision-making in RDMs by increasing loss-guided behavioural adaptation. Together, these findings identify parallel versus serial AIC-PLC processing as a potential neural mechanism underlying the tendency some individuals have to make suboptimal decisions.

neuroscience↗

bioRxiv2024

Compulsion derived from incentive cocaine-seeking habits is associated with a downregulation of the dopamine transporter in striatal astrocytes

The development of compulsive cue-controlled -incentive- drug-seeking habits, a hallmark of substance use disorder, is predicated on an intrastriatal shift in the locus of control over behaviour from a nucleus accumbens (Nac) core - dorsomedial striatum network to a Nac core - anterior dorsolateral striatum (aDLS) network. Such shift parallels striatal adaptations to chronic drug, including cocaine self-administration, marked by dopamine transporter (DAT) alterations originating in the ventral striatum that spread eventually to encompass the aDLS. Having recently shown that heroin self-administration results in a pan-striatal reduction in astrocytic DAT that precedes the development of aDLS dopamine-dependent incentive heroin-seeking habits we tested the hypothesis that similar adaptations occurr following cocaine exposure. We compared DAT protein levels in whole tissue homogenates, and astrocytes cultured from ventral and dorsal striatal territories of drug naive male Sprague Dawley rats to those of rats with a history of cocaine-taking or an aDLS dopamine-dependent incentive cocaine-seeking habit. Cocaine exposure resulted in a decrease in whole tissue and astrocytic DAT across all territories of the striatum. We further demonstrated that compulsive, i.e., punishment-resistant, incentive cocaine-seeking habits were associated with a reduction in DAT mRNA levels in the Nac shell, but not the Nac core-aDLS incentive habit system. Together with the recent evidence of heroin-induced downregulation of striatal astrocytic DAT, these findings suggest that alterations in astrocytic DAT may represent a common mechanism underlying the development of compulsive incentive drug-seeking habits across drug classes.

neuroscience↗

bioRxiv2020

The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse

The anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug-related behaviours is complex since in rats exposed to extended access to cocaine self-administration, the AIC was shown to exert a state-dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. Thus, we investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC, induced both prior to or after long-term exposure to extended access heroin self-administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham-surgeries, pre-exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.

neuroscience↗