Biology subjects

Ndiaye, N. A.

Publications and source records attributed to Ndiaye, N. A..

3 recordsLinked to original sources

bioRxiv2024

Relapse after intermittent access to cocaine: Discriminative cues more effectively trigger drug seeking than do conditioned cues

When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse. We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration. During 15-20 intermittent-access sessions, rats self-administered sucrose pellets or i.v. cocaine paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues. Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS-periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Additionally, presenting the DS-alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+. Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+, CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value. After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking.

animal behavior and cognition↗

bioRxiv2021

D-amphetamine maintenance therapy reduces cocaine use in female rats

Currently, there are no approved medications to treat cocaine addiction. In this context, d-amphetamine maintenance therapy is a promising pharmacological strategy to reduce cocaine use. In both male rats and human cocaine users, d-amphetamine treatment reduces cocaine taking and seeking. However, this has not been examined systematically in female animals, even though cocaine addiction afflicts both women and men, and the sexes can differ in their response to cocaine. Here, we determined how d-amphetamine maintenance therapy during cocaine self-administration influences cocaine use in female rats. In experiment 1, two groups of female rats received 14 intermittent access (IntA) cocaine self-administration sessions. One group received concomitant d-amphetamine maintenance treatment (COC + A rats; 5 mg/kg/day, via minipump), the other group did not (COC rats). After discontinuing d-amphetamine treatment, we measured responding for cocaine under a progressive ratio schedule, responding under extinction and cocaine-primed reinstatement of drug seeking. In experiment 2, we assessed the effects of d-amphetamine maintenance on these measures in already cocaine-experienced rats. To this end, rats first received 14 IntA cocaine self-administration sessions without d-amphetamine. They then received 14 more sessions now either with (COC/COC + A rats) or without (COC/COC rats) concomitant d-amphetamine treatment. In both experiments, d-amphetamine treatment did not influence cocaine-primed reinstatement of cocaine seeking. However, after d-amphetamine treatment, rats responded less for cocaine both under progressive ratio and extinction conditions. Thus, d-amphetamine treatment can both prevent and reverse increases in the motivation to take and seek cocaine in female animals.

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↗