Reinstatement of heroin or cocaine seeking by pharmacological agents that are different from the self-administered drug
| Neurotransmitter System | References | Procedure; Training Dose (mg/kg/infusion); Schedule; Session Duration (h/day) | Cocaine-Trained | Heroin-Trained |
|---|---|---|---|---|
| Acetylcholine | ||||
| Cholinergic agonist: | ||||
| Nicotine: (0.038–0.6 mg/kg, s.c.) | Schenk and Partridge, 1999 | W; 0.5; FR-1; 2 h | Some effect | |
| Nicotine: (0.05–0.1 mg/kg, i.v.) | Wise et al., 1990 | W; 1.0; FR-1; 2 h | No effect | |
| Adenosine | ||||
| Nonselective receptor antagonist: | ||||
| Caffeine (5.0–40.0 mg/kg, i.p.) | Worley et al., 1994 | W; 0.25; FR-1; 2 h | Reinstatement | |
| Caffeine (20.0 mg/kg, i.p.) | Schenk et al., 1996 | B-W; 0.25; FR-1; 2 h | Reinstatement | |
| Caffeine (1.25–20.0 mg/kg, i.p.) | Schenk and Partridge, 1999 | W; 0.5; FR-1; 2 h | Reinstatement | |
| Cannabinoids | ||||
| Cannabinoid agonist: | ||||
| Δ9-THC (0.3–3.0 mg/kg, i.p.) | Schenk and Partridge, 1999 | W; 0.5; FR-1; 2 h | No effect | |
| HU210 (4–100 μg/kg, s.c.) | De Vries et al., 2001 | B; 0.5; FR-5; 2 h | Reinstatement | |
| Dopamine | ||||
| Dopamine (30.0 μg/side, NAc) | Cornish and Kalivas, 2000 | B; 0.5–1.0; FR-1; 2 h | Reinstatement | |
| Indirect agonists: | ||||
| Amphetamine (1.0 mg/kg, i.p.) | De Vries et al., 1998a | B; H, 0.05; C, 0.5; FR-1; 2–3 h | Reinstatement | Reinstatement |
| Amphetamine (0.1–2.0 mg/kg, i.v.) | de Wit and Stewart, 1981 | W; 1.0; FR-1; 2–3 h | Reinstatement | |
| Amphetamine (0.3–3.0 mg/kg, i.p.) | Schenk and Partridge, 1999 | W; 0.5; FR-1; 2 h | Reinstatement | |
| Amphetamine (0.5 mg/kg, i.p.) | Sutton et al., 2000 | B; 1.0; FR-1; 4 h | Reinstatement | |
| Amphetamine (10.0 μg/side, NAc) | Stewart and Vezina, 1988 | W; 0.1; FR-1; 2–3 h | Reinstatement | |
| Cocaine (10.0 mg/kg, i.p.) | De Vries et al., 1998a | B; H, 0.05; C; 0.5; FR-1, 2–3 h | Reinstatement | Reinstatement |
| Cocaine (0.5–2.0 mg/kg, i.v.) | de Wit and Stewart, 1983 | W; 0.1; FR-1; 2–3 h | No effect | |
| Cocaine analogs: | ||||
| WIN 35,428 (0.1–3.0 mg/kg, i.p.) | Schenk et al., 2000 | W; 0.5; FR-5; 2 h | Reinstatement | |
| RTI-55 (0.05–0.5 mg/kg, i.p.) | Schenk et al., 2000 | W; 0.5; FR-5; 2 h | Reinstatement | |
| Nonselective DA agonist: | ||||
| Apomorphine (0.1–1.0 mg/kg, s.c.) | De Vries et al., 1999 | B; H, 0.05; C, 0.5; FR-1; 2–3 h | Suppression | Suppression |
| Apomorphine (0.0625–0.5 mg/kg, i.v.) | de Wit and Stewart, 1981 | W; C; 1.0; FR-1; 2–3 h | No effect | |
| DA reuptake inhibitor: | ||||
| GBR 12909 (10.0–20.0 mg/kg, i.p.) | De Vries et al., 1999 | B; H, 0.05; C; 0.5; FR-1; 2–3 h | Reinstatement | Reinstatement |
| GBR 12909 (3.0–30.0 mg/kg, i.p.) | Schenk et al., 2000 | W; 0.5; FR-5; 2 h | Reinstatement | |
| Methylphenidate (2.0–20.0 mg/kg, i.p.) | Schenk and Partridge, 1999 | W; 0.5; FR-1; 2 h | Reinstatement | |
| D1-like receptor agonist: | ||||
| SKF 82958 (1.0 mg/kg, s.c.) | De Vries et al., 1999 | B; H, 0.05; C, 0.5; FR-1; 2–3 h | No effect | No effect |
| SKF 82958 (0.3 or 1.0 mg/kg, s.c.) | Self et al., 1996 | W; 0.05; FR-1, 2 h | No effect | |
| D2-like receptor agonist: | ||||
| Quinpirole (0.5 mg/kg, s.c.; prolonged withdrawal) | De Vries et al., 1999 | B; H, 0.05; C, 0.5; FR-1; 2–3 h | Reinstatement | No effect |
| Quinpirole (0.05–1.0 mg/kg, s.c.; early withdrawal) | De Vries et al., 2002 | B; H, 0.05; C, 0.5; FR-1; 2–3 h | Reinstatement | Reinstatement |
| Quinpirole (0.03–3.0 mg/kg, i.p.) | Self et al., 1996 | W; 0.05; FR-1, 2 h | Reinstatement | |
| Bromocriptine (0.5–2.0 mg/kg, i.v.) | Wise et al., 1990 | W; H, 0.1; C, 1.0; FR-1; 2 h | Reinstatement | Reinstatement |
| D2/3-like receptor agonist: | ||||
| 7-OH-DPAT (0.3 mg/kg, s.c.) | Self et al., 1996 | W; 0.05; FR-1, 2 h | Reinstatement | |
| GABA | ||||
| GABAB agonist: | ||||
| Baclofen (1.25–2.5 mg/kg, i.p.) | Campbell et al., 1999 | W; 0.4; FR-1, 7 h | No effect | |
| Others | ||||
| Ethanol (1.0–10.0 mg/kg, i.v.) | de Wit and Stewart, 1981 | W; 1.0; FR-1; 2–3 h | No effect | |
| Ethanol (2.0 g/kg, i.v.) | Wise et al., 1990 | W; 1.0; FR-1; 2 h | No effect | |
| Methohexital (1.0–2.0 mg/kg, i.v.) | de Wit and Stewart, 1981 | W; 1.0; FR-1; 2–3 h | No effect | |
| Methohexital (0.5–1.0 mg/kg, i.v.) | Wise et al., 1990 | W; 1.0; FR-1; 2 h | No effect | |
| Glutamate | ||||
| AMPA receptor agonist: | ||||
| AMPA (0.4 nmol/side, NAc) | Cornish and Kalivas, 2000 | B; 0.5–1.0; FR-1; 2 h | Reinstatement | |
| AMPA (0.04–0.4 nmol/side, NAc) | Cornish et al., 1999 | B; 0.5–1.0; FR-1; 2 h | Reinstatement | |
| NMDA agonist: | ||||
| NMDA (83.0 pmol/side, VTA) | Vorel et al., 2001 | B; 1.0; FR-1; 3 h | Reinstatement | |
| cis-ACDA (1.0–3.0 nmol/side, NAc) | Cornish et al., 1999 | B; 0.5–1.0; FR-1; 2 h | Reinstatement | |
| NMDA antagonist: | ||||
| MK-801 (0.1–0.25 mg/kg, i.p.) | De Vries et al., 1998b | B; 0.5; FR-1; 2–3 h | Reinstatement | |
| Noradrenaline | ||||
| α 2-Adrenoceptor agonist: | ||||
| Clonidine (0.0625 or 0.125, i.v.) | Wise et al., 1990 | B; 1.0; FR-1; 2 h | No effect | |
| Opioids | ||||
| Agonists: | ||||
| Morphine (0.3–3.0 mg/kg, i.p.) | de Wit and Stewart, 1981 | W; 1.0; FR-1; 2–3 h | No effect | |
| Morphine (0.1–10.0 mg/kg, i.p.) | Schenk and Partridge, 1999 | W; 0.5; FR-1; 2 h | No effect | |
| Morphine (18.0 μg, VTA) | Stewart, 1984 | W; H, 0.1; C, 1.0; FR-1; 2–3 h | Reinstatement | Reinstatement |
| Morphine (5.0 or 10.0 μg, NAc) | Stewart and Vezina, 1988 | W; 0.1; FR-1; 2–3 h | No effect | |
| Heroin (0.05–0.2 mg/kg, i.v.) | de Wit and Stewart, 1981 | W; 1.0; FR-1; 2–3 h | No effect | |
| Heroin (0.25 mg/kg, s.c.) | De Vries et al., 1998a | B; H, 0.05; C, 0.5; FR-1; 2–3 h | No effect | Reinstatement |
| Butorphanol (8.0 mg/kg, s.c.) | Lynch et al., 1998 | W; 0.4; FR-1, 7 h | No effect | |
| Partial agonist: | ||||
| Buprenorphine (0.025–0.4 mg/kg, i.v.) | Comer et al., 1993 | W; 0.2–1.0; FR-1; 24 h | No effect | |
| μ-Receptor selective agonist: | ||||
| Etonitazene (2.5 or 5.0 mg/kg, i.v.) | Comer et al., 1993 | W; 1.0; FR-1; 24 h | No effect | |
| Preferential μ-receptor antagonist: | ||||
| Naltrexone (1.0–5.0 mg/kg, i.p.) | Stewart and Wise, 1992 | W; 0.1; FR-1; 3 h | No effect | |
| Naltrexone (1.6 or 3.2 mg/kg, i.v.) | Comer et al., 1993 | W; 1.0; FR-1; 24 h | No effect | |
| Naltrexone (0.1 mg/kg, s.c., with heroin minipumps) | Shaham et al., 1996 | B; 0.1; FR-1; 7–12 h | No effect | |
| Other manipulations | ||||
| PKA inhibitor: | ||||
| Rp-cAMPS (40.0 or 80.0 nmol/side, NAc) | Self et al., 1998 | W; 0.5; FR-1; 2 h | Reinstatement | |
| PKA activator: | ||||
| Sp-cAMPS (40.0 or 80.0 nmol/side, NAc) | Self et al., 1998 | W; 0.5; FR-1; 2 h | Nonspecific activation |
Abbreviations: B, between-session reinstatement procedure; B-W, between-within session reinstatement procedure; C, cocaine; FR, fixed ratio schedule of reinforcement; H, heroin; W, within-session reinstatement procedure.