Cues Paired with either Rapid or Slower Self-Administered Cocaine Injections Acquire Similar Conditioned Rewarding Properties

Abstract

The faster drugs of abuse reach the brain, the more addictive they can be. It is not known why this is. Environmental stimuli associated with drugs can promote the development and persistence of addiction by invigorating and precipitating drug-seeking behaviour. We determined, therefore, whether cues associated with the self-administration of rapidly delivered cocaine (injected intravenously over 5 versus 90 seconds) would acquire greater conditioned rewarding properties, as assessed by the performance of an operant response reinforced solely by the cues. Rats nose-poked for intravenous cocaine infusions delivered either over 5 or 90 seconds. Discrete visual cues accompanied each infusion. The rats could then press a lever to obtain the cues—now a conditioned reward—or an inactive lever. Rats in both the 5- and 90-second groups pressed more on the active versus inactive lever following extensive (24 sessions) but not following limited (3 sessions) self-administration training. There were no group differences in this behaviour. Following withdrawal from cocaine self-administration, lever discrimination progressively abated in both groups and was lost by withdrawal day 30. However, the rewarding properties of the cues were not “forgotten” because on withdrawal days 32–33, amphetamine selectively enhanced active-lever pressing, and did so to a similar extent in both groups. Thus, cues paired with rapid or slower cocaine delivery acquire similar conditioned rewarding properties. We conclude, therefore, that the rapid delivery of cocaine to the brain promotes addiction by mechanisms that might not involve a greater ability of drug cues to control behaviour.

Revisiting long‐access versus short‐access cocaine self‐administration in rats: intermittent intake promotes addiction symptoms independent of session length

“…Male Wistar rats ( n = 27, 225–250 g; Charles River Laboratories, St Constant, QC) were housed individually under a reverse 12 hours–12 hours dark–light cycle (Lights off at 8:30 AM) in a temperature‐controlled and humidity‐controlled room. After 4–5 days of habituation to the animal colony, rats were implanted with a catheter into the jugular vein, as described previously (Samaha, Minogianis, & Nachar ). Water was available ad libitum and food was restricted to 25 g/day.…”

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

“…Once rats met this acquisition criterion, they were switched to FR3 for at least 2 sessions. When rats reliably self-administered food pellets (∼ 25 pellets/session, on two consecutive sessions), they were and implanted with catheters into the jugular vein (Samaha, Minogianis & Nachar, 2011; Weeks, 1962). Following recovery, rats learned to self-administer cocaine (0.25 mg/kg/injection; Medisca Pharmaceutique, St Laurent, QC; dissolved in 0.9% saline, delivered over 5 s, with a 20-s timeout), as described in Allain, Bouayad-Gervais & Samaha (2018).…”

Amphetamine Maintenance Therapy During Intermittent Cocaine Self-Administration in Rats: Reduction of Addiction-like Behavior is Associated with Attenuation of Psychomotor and Dopamine Sensitization

“…On the day following the end of food training, catheters were implanted into the jugular vein of the rats (75)(76)(77), under isofluorane anesthesia (5% for induction, 2-3% for maintenance). Homemade catheters consisted of a 12.5-cm length of silastic tubing linked to a stainless-steel cannula (C313G-5UP).…”