Biology subjects

Algallal, H.

Publications and source records attributed to Algallal, H..

4 recordsLinked to original sources

bioRxiv2025

Intermittent Cocaine Use Patterns, Not Total Intake, Predict Cue-induced Drug Seeking in Rats

Background and purposeCocaine-associated cues trigger relapse to drug use in humans and animal models. In rats, long daily cocaine access (4-6 h vs. 1-2 h) increases drug self-administration and cue-induced cocaine seeking, suggesting that greater intake promotes relapse. However, prior studies used continuous-access paradigms, whereas human cocaine use is typically intermittent. Moreover, these studies used conditioned stimuli (CS), whereas discriminative stimuli (DS) are more effective in triggering increases in drug-seeking actions. Here, we used intermittent access (IntA) self-administration to examine how session length (Short-IntA: 2 h vs. Long-IntA: 4 h) affects CS- and DS-induced cocaine seeking. Experimental approachFemale rats self-administered cocaine intermittently during daily 2- or 4-h IntA sessions, with alternating DS+ (cocaine available; 5 min) and DS- (no cocaine; 25 min) periods. Lever pressing during DS+ delivered cocaine and a CS+; lever pressing during DS-delivered only a CS-. After four weeks of abstinence, rats received a cocaine-seeking test where all cues were presented response-independently, and lever presses - which had no consequence - measured cocaine seeking. Key resultsLong-IntA rats took twice more cocaine than did Short-IntA rats. Both groups later showed significant (DS+)-but not (CS+)-triggered cocaine seeking, with no group differences. Thus, total intake did not predict cue-induced relapse propensity. However, individual cocaine intake patterns did (hourly consumption, burst-like self-administration, and latency to first infusion). Conclusions and ImplicationsUnder intermittent-access conditions, individual cocaine-use patterns, not cumulative intake, predict vulnerability to cue-induced relapse. This highlights the importance of individual drug-taking profiles in relapse risk assessment.

animal behavior and cognition↗

bioRxiv2025

Activation of Infralimbic cortex neurons projecting to the nucleus accumbens shell suppresses discriminative stimulus-triggered relapse to cocaine seeking in rats

Cocaine addiction is marked by high relapse rates, often triggered by drug-associated cues. These cues can be conditioned stimuli (CSs), which occur after drug intake and are paired with drug effects, and discriminative stimuli (DSs), which signal drug availability, regardless of ongoing drug-seeking behaviour. While projections from the infralimbic cortex (IL) to the nucleus accumbens (NAc) shell are known to regulate CS-induced cocaine relapse, their role in DS-triggered relapse is not known. To investigate this, we examined how activating IL[->]NAc shell projections influences relapse driven by DSs and CSs during abstinence from intermittent cocaine use. Female Sprague-Dawley rats received viral-mediated gene expression of excitatory designer receptors exclusively activated by designer drugs in the IL. Rats then self-administered cocaine during 12 intermittent-access sessions (5-min cocaine ON/25-min cocaine OFF, 4h/day). A discrete light (DS+) signalled drug-available periods, while a different light (DS-) signalled drug non-availability. During each DS+ period, cocaine infusions were paired with a compound light-tone (CS+). Four weeks later, rats were tested for cue-induced cocaine seeking following response-independent presentation of DS+, CS+ or both. Immediately prior to testing, rats received intra-NAc shell clozapine N-oxide or aCSF to activate IL terminals. DS+ alone and DS+/CS+ combined triggered greater cocaine seeking than did the CS+. Activation of IL[->]NAc shell projections suppressed relapse behaviour in DS+ and DS+/CS+ conditions. These findings highlight the distinct and powerful influence of DSs on relapse and identify the IL[->]NAc shell circuit as a promising target for relapse prevention.

neuroscience↗

bioRxiv2023

Intermittent Nicotine Access is as Effective as Continuous Access in Promoting Nicotine Seeking and Taking in Rats

Nicotine is a principal psychoactive agent in tobacco, contributing to tobaccos addictive potential. Preclinical studies on the effects of voluntary nicotine intake typically use self-administration procedures that provide continuous nicotine access during each self-administration session. However, many smokers consume cigarettes intermittently rather than continuously throughout each day. For drugs including cocaine and opioids, research in laboratory rats shows that intermittent intake can be more effective than continuous intake in producing patterns of drug use relevant to addiction. We asked, therefore, how intermittent versus continuous nicotine self-administration influences nicotine seeking and taking behaviours. Female and male rats had continuous (i.e., Long Access; LgA, 6 h/day) or intermittent (IntA; 12 min ON, 60 min OFF, for 6 h/day) access to intravenous nicotine (15 {micro}g/kg/infusion), for 12 daily sessions. We then assessed intake, responding for nicotine under a progressive ratio schedule of drug reinforcement and cue- and nicotine-induced reinstatement of drug seeking. We also estimated nicotine pharmacokinetic parameters during LgA and IntA self-administration. Overall, LgA rats took twice more nicotine than did IntA rats, yielding more sustained increases in estimated brain concentrations of the drug. However, the two groups showed similar motivation to seek and take nicotine, as measured using reinstatement and progressive ratio procedures, respectively. Thus, intermittent nicotine use is just as effective as continuous use in producing addiction-relevant behaviours, despite significantly less nicotine exposure. This has implications for modeling nicotine self-administration patterns in human smokers and resulting effects on brain and behaviour.

neuroscience↗

bioRxiv2018

Sex differences in cocaine self-administration behaviour under Long Access versus Intermittent Access conditions

A widely accepted rodent model to study cocaine addiction involves allowing animals continuous access to drug during long self-administration sessions ( Long-access or LgA). This produces continuously high brain concentrations of drug during each session. This might not model the pharmacokinetics of cocaine use in experienced human users, which are thought to involve intermittently spiking brain cocaine concentrations within and between bouts of use. Intermittent-access (IntA) cocaine self-administration models this spiking pattern in rats. IntA is also particularly effective in increasing incentive motivation for drug. Most IntA studies have been conducted in male rats. Both humans and non-human animals can show sex differences in all phases of the addiction process. We compared cocaine use in female and male rats that self-administered the drug (0.25 mg/kg/injection, i.v.) during 10 daily, 6-h LgA or IntA sessions. Cocaine intake was greatest under LgA, and female LgA rats escalated their intake. However, only IntA rats (both sexes) developed locomotor sensitization to self-administered cocaine and sensitization was greatest in the females. Five and 25 days after the last self-administration session, we quantified incentive motivation for cocaine by measuring breakpoints for the drug (0.083-0.75 mg/kg/injection) under progressive ratio. Breakpoints were similar in IntA and LgA rats. There were no sex differences in breakpoints under LgA. However, under IntA, females reached higher breakpoints for cocaine than males. Thus, LgA might be best suited to study sex differences in cocaine intake, while IntA might be best suited to study sex differences in incentive motivational processes in cocaine addiction.

neuroscience↗