Reference | Drugs Evaluated for Opioid Withdrawal Outcomes (Dose and Route)a | Species | Sample Size | Withdrawal Method | Dependence Method | Withdrawal Signs Assessed | Summary of Withdrawal-Specific Results |
---|---|---|---|---|---|---|---|
Ahmadi-Soleimani et al. (2014) | SB-334867 (100 µM/0.2 µl). Direct administration to LPGi nucleus. | Rat | 8–13 | Precipitated, naloxone (2 mg/kg, i.p.). Injection occurred following morphine escalation, specific time NR | Escalating mrophine (drinking water) increasing in concentrations up to 0.4 mg/ml and maintained for 15 days | Chewing, defecation, digging, genital licking, grooming, rearing, sniffing, teeth chattering, and wet dog shakes | SB-334867 decreased chewing, genital licking, grooming, rearing, and sniffing. |
Azizi et al. (2010) | SB-334867 (100 µM/0.2 µl). Direct administration to locus coereleus. | Rat | 9 | Precipitated, naloxone (1 mg/kg, i.p.) 2 hours after morphine administration on day 10 | Morphine (10 mg/kg) delivered every 12 hours for 10 days | Chewing, diarrhea, head tremor, jumping, rearing, scratching, sniffing, teeth chattering, ptosis, and wet dog shakes | SB-334867 decreased chewing, diarrhea, head tremor, scratching, teeth chattering, and wet dog shakes. |
Davoudi et al. (2016) | SB-334867 (3 mM/0.2 µl). Bicuculline (15 µM/0.2 µl). Direct administration to locus coereleus. | Rat | 7 | Precipitated, naloxone (3 mg/kg, s.c.) on day 8 | Escalating morphine doses up to 66 mg/kg, s.c., by day 7 | Defecation, head tremor, genital licking, rearing, scratching, sniffing, teeth chatttering, wet dog shake, and writhing | SB-334867 decreased defecation, head tremor, gential licking, rearing, scratching, sniffing, wet dog shakes, and writhing. Bicuculline (GABA antagonist) had no effect by itself but when coadministered with SB-334867 reversed effects on head tremor, rearing, scratching, teeth chattering, wet dog shakes, and writhing. |
Erami et al. (2012) | SB-334867 (1 mM/5 µl). Administered intracerebroventricularly. | Rat | 8 | Precipitated, nalozone (2 mg/kg, s.c.) on day 10 | Morphine (10 mg/kg, s.c.) delivered every 12 hours for 10 days | Chewing, climbing, defecation, diarrhea, head tremor, jumping, rearing, scratching, sniffing, teeth chattering, and wet dog shakes | SB-334867 decreased chewing, climbing, diarrhea, jumping, rearing, rhinorrhea, and teeth chattering. |
Ghaemi-Jandabi et al. (2014) | Orexin A (100 µM/200 nl); SB-334867 (100 µM/200 nl). Direct administration to locus coereleus. | Rat | 6 to 7 | Precipiated, OXA (0.2 µl) injection to locus coereleus on day 10 | Morphine (10 mg/kg, s.c.) delivered every 12 hours for 9 days | Chewing, head tremor, paw tremor, rearing, scratching, sniffing, teeth chattering, and wet dog shakes | OXA increased chewing, head tremor, rearing, scratching, and wet dog shakes. SB-33847 decreased chewing, head tremor, paw tremor, scratching, sniffing, rearing, and teeth chattering. |
Hooshmand et al. (2017) | SB-334867 (3 mM/200 nl) + glutamate (100 nM/200 nl). Direct administration to locus coereleus. | Rat | NR | Precipitated, glutamate (100 nM/200 nl) injection to locus coereleus on day 7 | Escalating morphine up to 66 mg/kg, s.c., by day 7 | Chewing, defecation, head tremor, paw tremor, rearing, scratching, sniffing, teeth chattering, wet dog shakes, and writhing | Glutamate increased chewing, paw tremor rearing, scratching, sniffing, wet dog shakes, and writhing. SB-334867 pretreatment did not attenuate glutamate-precipitated withdrawal during the day (rest phase) but decreased chewing, head tremor, paw tremor, rearing, sniffing, scratching, teeth chattering, wet dog shakes, and writhing during the night (active phase). |
Hooshmandi et al. (2017) | SB-334867 (0.5 µg/0.5 µl). Direct administration to dorsal hippocampus. | Rat | 12 | Precipitated, naloxone (1.5 mg/kg, i.p.) on day 10 | Morphine (10 mg/kg, s.c.) delivered every 12 hours for 9 days. | Activity, chewing, diarrhea, head tremor, freezing, penile licking, ptosis, rearing, rubbing, scratching, sniffing, teeth chattering, wet dog shakes, and writhing | SB-334867 decreased chewing, diarrhea, freezing, penile licking, ptosis, scratching, teeth chattering, wet dog shakes, and writhing. |
Laorden et al. (2012) | SB-334867 (20 mg/kg). Administered intraperitoneally. | Rat | 4–8 | Precipitated, naloxone (1 mg/kg, s.c.) on day 6 | Morphine (150 mg) subcutaneous implant for 6 days | Diarrhea, jumping, mastication, paw tremor, piloerection, ptosis, sniffing, teeth chattering, tremor, wet dog shakes, and writhing | SB-334867 decreased body tremor, diarrhea, mastication, piloerection, ptosis, sniffing, wet dog shakes, and writhing. Global withdrawal score also decreased. |
Sharf et al. (2008) | SB-334867 (0, 20 mg/kg). Direct administration to nucleus accumbens. | Mouse | 9 | Precipitated, naloxone (1 mg/kg, s.c.) 2 hours after morphine administration | Escalating morphine doses up to 100 mg/kg, i.p., for 2.5 days | Backward walking, gnawing, head swoops, jumping, paw tremors, ptosis, tremors, and wet dog shakes | SB-334867 decreased backward walking, ptosis, tremors, wet dog shakes, and global withdrawal score (sum of withdrawal symptoms). |
LPGi, lateral paragigantocellularis; NR, not reported.
↵a All drugs were administered to specific brain regions, except where noted.