TABLE 4

Relapse after electric barrier–induced voluntary abstinence: summary of main findings

No.ReferenceGeneral Training ProceduresTestMajor Findings
1Cooper et al. (2007)Rat strain and sex
Sprague-Dawley males.
Drug training
0.5 mg/kg/infusion of cocaine (FR1 to FR2) for 10–13 sessions (3 h, limit of 35 infusions per session).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered (0.25 mA, increasing to 0.45 mA).
Relapse test
30-min sessions of noncontingent drug-cue exposure while the electric barrier was active (n = 24).
Large individual differences in cue-induced relapse to cocaine seeking after electric barrier–induced abstinence; relapse tests were performed in the presence of the barrier in this study and in studies 2–4 below.
2Barnea-Ygael et al. (2012)Rat strain and sex
Sprague-Dawley males.
Drug training
0.5 mg/kg/infusion of cocaine (FR1 to FR2) for 11–15 sessions (3 h, limit of 35 infusions per session).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered (increasing intensity until three consecutive sessions of abstinence).
Forced abstinence
Rats undergoing electric barrier–induced abstinence returned to home cage for 14 days of forced abstinence.
Relapse test
Cue-induced reinstatement for 3 h conducted 1 or 14 days after three consecutive sessions of abstinence with electric barrier active or at 85% intensity (n = 11 day 1; n = 10 day 14).
Cue-induced relapse to cocaine seeking after electric barrier–induced abstinence is lower after 14 days of home-cage forced abstinence than after 1 day.
3Peck et al. (2013)Rat strain and sex
Long-Evans males.
Drug training
0.5 mg/kg/infusion of cocaine or 0.05 mg/kg/infusion of heroin (FR1) for 15 sessions (3 h, no limit noted).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered (0.25 mA, increasing by 0.04 mA intensity until three consecutive sessions of abstinence).
Relapse test
30-min sessions of noncontingent drug-cue exposure while the electric barrier was on (n = 10 heroin noncontingent cue; n = 10 heroin no noncontingent cue; n = 8 cocaine noncontingent cue).
The proportion of heroin-trained male rats that demonstrate discrete cue–induced drug seeking after electric barrier–induced abstinence is higher than that of cocaine-trained rats.
4Saunders et al. (2013)Rat strain and sex
Sprague-Dawley males.
Pavlovian training
Rats were screened for sign tracking or goal tracking prior to drug training phase, according to three measures of Pavlovian conditioned approach following CS-US pairings (VT90, 25 trials).
Drug training
0.4 mg/kg/infusion cocaine (FR1) for 10 infusions (three sessions), then 20 infusions per session (three sessions), and finally 40 infusions per session (five sessions). Rats were further divided into two groups: paired (drug delivery paired with light cue) and unpaired (cue light presented randomly).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered and continuous mild foot shock (0, 0.15, 0.20, 0.25 mA, or increased by 0.05 mA) until they earned fewer than five infusions (30-min session).
Forced abstinence
Rats undergoing electric barrier–induced abstinence returned to home cage for 2 weeks of forced abstinence.
Relapse tests
Test for cocaine seeking for 30 min with foot shock on but at 50% intensity each rat had reached during training.
Cocaine seeking (n = 10 sign-trackers and n = 10 goal-trackers for paired; n = 8 sign-trackers and n = 7 goal-trackers for unpaired) with additional tests for effect of vehicle or flupentixol (20 µg/0.5 µl/side; n = 8 sign-trackers and n = 6–7 goal-trackers per condition), or vehicle or amphetamine (10 µg/0.5 µl/side; n = 7–8 sign-trackers and n = 6–7 goal-trackers per condition).
Cue-induced cocaine seeking after electric barrier–induced abstinence is stronger and more reliable in sign-tracking male rats than in goal-tracking rats; NAc core injections of Drd1-Drd2 antagonist (flupentixol) and amphetamine decrease and increase, respectively, cue-induced cocaine seeking.
5Fredriksson et al. (2020)Rat strain and sex
Sprague-Dawley males and females.
Drug training
0.1 mg/kg/infusion oxycodone (FR1) for 14 sessions (6 h, limited to 15 infusions per hour).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered and continuous mild foot shock (0 mA, increased by 0.1 mA until 0.4 mA) for 14 or 28 sessions (2 h).
Forced abstinence
Separate group of home-cage forced abstinence for 14 or 28 days.
Relapse tests
Test for oxycodone seeking for 30 min on abstinence day 1, and 15 or 30 with foot shock off for effect of incubation of oxycodone craving (n = 14–28 males and n = 12–25 females per abstinence condition and day) with additional tests of (−)-OSU6162 (vehicle, 7.5 or 15 mg/kg, s.c.) after electric barrier–induced abstinence (n = 9–13 males and n = 9–15 females per dose and abstinence day) or after forced abstinence (n = 10–11 males and n = 9 females per dose).
Male and female rats show stronger incubation of oxycodone craving after electric barrier–induced abstinence than after home-cage forced abstinence. Systemic injections of (−)-OSU6162, a dopamine stabilizer, decrease incubated oxycodone seeking in both male and female rats after electric barrier–induced abstinence but only in male rats after forced abstinence. No sex differences were observed in oxycodone self-administration or electric barrier–induced abstinence.
6Ewing et al. (2021)Rat strain and sex
Long-Evans males
Drug training
0.05 mg/kg/infusion of heroin (FR1) for 15 sessions (3 h).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered and continuous mild foot shock (0.25 mA, increasing by 0.07 mA intensity until three consecutive 30-min sessions of abstinence).
Relapse test
Test for cue-induced heroin seeking in 30-min sessions (noncontingent heroin-cue exposure and contingent heroin-cue exposure (FR2) with electric barrier set to 25% intensity). 30-min pretreatment (intraperitoneal) with NGB 2904 (n = 45 vehicle, 0.25, 1, 1.5, or 2 mg/kg), SKF 77434 (n = 40 vehicle, 0.25, 1, or 2 mg/kg), or NGB 2904 + SKF 77434 combination (n = 42 0.25 + 0.25, 0.25 + 0.5, 1 + 0.25, or 1 + 0.5 mg/kg).
Systemic injections of a combination of low doses of NGB 2904 (Drd3 receptor antagonist) and SKF 77434 (Drd1 receptor partial agonist) decrease cue-induced heroin seeking more effectively than either compound alone.
7Fredriksson et al. (2021)Rat strain and sex
Sprague-Dawley males and females.
Fos-lacZ males and females.
Drug training
0.1 mg/kg/infusion oxycodone (FR1) for 14 sessions (6 h, limited to 15 infusions per hour).
Electric barrier
Application of an electric barrier that covers two-thirds of the chamber closest to lever that results in a continuous foot shock if entered and continuous mild foot shock (0.4 mA, starting at 0.0 mA increasing by 0.1 mA) for 13 or 16 days.
Daun02 induction
Short (15 min) oxycodone context or novel context exposure followed by injections of vehicle or Daun02.
Relapse tests
Test for oxycodone seeking for 30-min or 90-min sessions on abstinence day 1, 15, or 18 with foot shock off for vSub Fos expression (n = 6–7 per no test versus test), vehicle or muscimol + baclofen after electric barrier (50 + 50 ng/0.5 µl/side) injections in vSub (n = 10–14 per day 1 versus day 15), vehicle or muscimol + baclofen forced abstinence (50 + 50 ng/0.5 µl/side) injections in vSub (n = 16–18 per dose), and Daun02 (0.4 μg/side) inactivation (n = 12–17 per context and dose).
Relapse to oxycodone seeking is associated with increased vSub Fos expression. vSub injections of muscimol + baclofen or Daun02 decrease incubation of oxycodone seeking after electric barrier–induced abstinence but not forced abstinence.
  • CNO, clozapine-N-oxide; CS, conditioned stimulus; FR, fixed ratio; US, unconditioned stimulus; VT, variable time.