Biology subjects

Hynes, T. J.

Publications and source records attributed to Hynes, T. J..

3 recordsLinked to original sources

bioRxiv2026

Chemogenetic inhibition of the noradrenergic locus coeruleus promotes the development of risk-taking decisional strategies and selectively enhances motor impulsivity in females

The locus coeruleus noradrenaline (LC-NA) system is a key regulator of arousal, attention, and reward learning. Noradrenaline plays a critical role in impulse control, and recent evidence indicates the importance of noradrenaline signaling in cost-benefit decision making once choice strategies are established. However, whether the LC causally shapes the acquisition of decision strategies, and how this contribution may differ across sexes, remains unclear. We addressed these questions by chemogenetically inhibiting catecholaminergic neurons within the LC of adult tyrosine-hydroxylase Cre (TH::Cre) rats (n=69; 35 females) throughout acquisition of the cued rat gambling task (crGT), a probabilistic decision making paradigm that incorporates salient audiovisual reward-paired cues and simultaneously measures motor impulsivity. LC inhibition accelerated the development of risky choice strategies early in training in both males and females, reflected by impaired adoption of the most advantageous option and increased preference for risky options. Trial-by-trial analyses reveal that LC inhibition promoted switches in choice strategy following safe wins, while reducing switches away from risky options after both wins and losses. LC inhibition therefore seemed to encourage the repetition of actions that resulted in more uncertain outcomes. LC inhibition also selectively enhanced motor impulsivity in females, particularly early in training. These results provide causal evidence that the LC system guides the formation of optimal decisional strategies, while exerting sex-specific control over impulsive action. Abbreviated summaryChernoff et al. demonstrate that noradrenergic locus coeruleus (LC) neurons are required to develop optimal decisional strategies, as their inhibition hastens the adoption of risk-preferring choice tendencies. This may be underpinned by reduced behavioural sensitivity to likely outcomes. They also show that the LC regulates impulse control, specifically in females.

neuroscience↗

bioRxiv2022

Biological Sex Influences the Contribution of Sign-Tracking and Anxiety-Like Behaviour toward Remifentanil Self-Administration

Most people sample addictive drugs, but use becomes disordered in only a small minority. Two important factors that influence susceptibility to addiction are individual differences in personality traits and biological sex. The influence of traits on addiction-like behaviour is well characterized in preclinical models of cocaine self-administration, but less is understood in regards to opioids. How biological sex influences trait susceptibility to opioid self-administration is likewise less studied than psychostimulants. Thus, we sought to elucidate how biological sex and several addiction-relevant traits interact with the propensity to self-administer the opioid remifentanil. We first screened female (n=19) and male (n=19) rats for four addiction-relevant traits: impulsivity, novelty place-preference, anxiety-like behaviour, and attribution of incentive value to reward cues. Rats were then trained to self-administer remifentanil in a "conflict model" of drug self-administration. Rats had to endure a mild electric shock to access the response manipulandum that triggered an intravenous infusion of remifentanil. In male rats, high anxiety-like behaviour was positively correlated with the number of drug infusions if the shock level was low or completely absent. In females, sign-tracking was predictive of greater resistance to punishment during drug seeking; an effect that was mediated by anxiety-like behaviour. Females consumed more remifentanil under all conditions, and their drug seeking persisted in the face of significantly greater current than males. These findings demonstrate that the influence of behavioural traits over the propensity to self-administer opioids is dependent upon biological sex.

neuroscience↗

bioRxiv2022

Audiovisual cues must be predictable and win-paired to drive risky choice

Risky or maladaptive decision making is thought to be central to the etiology of both drug and gambling addiction. Salient audiovisual cues paired with rewarding outcomes, such as the jackpot sound on a win, can enhance disadvantageous, risky choice in both rats and humans, yet it is unclear which aspects of the cue-reward contingencies drive this effect. Here, we implemented six variants of the rat Gambling Task (rGT), in which animals can maximise their total sugar pellet profits by avoiding options paired with higher per-trial gains but disproportionately longer and more frequent time-out penalties. When audiovisual cues were delivered concurrently with wins, and scaled in salience with reward size, significantly more rats preferred the risky options as compared to the uncued rGT. Similar results were observed when the relationship between reward size and cue complexity was inverted, and when cues were delivered concurrently with all outcomes. Conversely, risky choice did not increase when cues occurred randomly on 50% of trials, and decision making actually improved when cues were coincident with losses alone. As such, cues do not increase risky choice by simply elevating arousal, or amplifying the difference between wins and losses. It is instead important that the cues are reliably associated with wins; presenting the cues on losing outcomes as well as wins does not diminish their ability to drive risky choice. Computational analyses indicate reductions in the impact of losses on decision making in all rGT variants in which win-paired cues increased risky choice. These results may help us understand how sensory stimulation can increase the addictive nature of gambling and gaming products.

animal behavior and cognition↗