TABLE 2

Preclinical examinations of the dopamine system on the opioid withdrawal syndrome

Only results pertaining to effects of non-opioid drugs on opioid withdrawal symptoms are presented.

ReferenceDrugs Evaluated for Opioid Withdrawal Outcomes (Dose and Route)SpeciesSample SizeWithdrawal MethodDependence MethodWithdrawal Signs AssessedSummary of Withdrawal-Specific Results
Ary and Lomax (1976)Apomorphine (20 µg); Dopamine (10, 50, 100, and 200 µg), Pimozide (0.5 and 1 µg, i.p.). Administered to rostral hypothalamus and lateral ventricle unless indicated.Rat≥5Precipitated, naloxone (1 mg/kg; i.p.) on day 3Morphine (75 mg) subcutaneous implantBody temperatureRostral hypothalamus injections: apomorphine (D2 agonist; 20 µg) increased the hypothermia produced by naloxone, pimozide (D2 antagonist; 0.5 and 1 µg) and dopamine had no effect. Lateral ventricle injections: no effects on naloxone-induced hypothermia.
Cox et al. (1976)Apomorphine (1.25 mg/kg) and pimozide (0.5 mg/kg) administered intraperitoneally; pimozide (0.5 µg) administered intracerebroventricularly.RatNRPrecipitated, naloxone (1 mg/kg; i.p.) on day 3Morphine (75 mg) subcutaneous implantBody temperature, chewing, diarrhea, head shakes, facial tremor, grooming, licking, sneezing, teeth chatter, wet dog shakes, and writhing. Total withdrawal scoreApomorphine (D2 agonist) (1.25 mg/kg, i.p.) decreased chewing, teeth chattering, wet dog shakes, and writhing. Pimozide (D2 antagonist) (0.5 mg/kg, i.p.) reduced hypothermia and increased chewing, head shakes, and writhing. Intracerebroventricularly: pimozide (0.5 µg, i.p.) significantly blocked hypothermia.
el-Kadi and Sharif (1998)Apomorphine (0.5, 1, 2.5, 5, 10, 20, and 30 mg/kg); L-DOPA (100 and 500 mg/kg); haloperidol (0.2 and 1.0 mg/kg); pimozide (2 and 5 mg/kg); domperidone (5 and 10 mg/kg); flupenthixol (0.05 and 0.1 mg/kg); sulpride (5 mg/kg). Administered intraperitoneally.Mouse8–10Precipitated, naloxone (1 mg/kg, i.p.) on day 7Escalating morphine doses up to 160 mg/kg, s.c., by day 6Body temperature, body weight, burrows, jumping, and wet dog shakesL-DOPA (dopamine precursor) (100 and 500 mg/kg) reduced jumping, burrows, body weight loss, hypothermia (100 and 500 mg/kg), and wet dog shakes (500 mg/kg). Apomorphine (D2 agonist) increased burrows and jumping at low doses (2.5 and 5 mg/kg) and decreased them at high doses (10, 20, and 30 mg/kg). Apomorphine also decreased body weight loss (2.5, 5, and 10 mg/kg) and increased wet dog shakes (2.5, 5, 10, and 20 mg/kg) and hypothermia (all doses). Haloperidol (D2 antagonist) reduced jumps (0.2 and 1 mg/kg), wet dog shakes (0.2 and 1 mg/kg), burrows (0.2 and 1 mg/kg), and body weight loss (1 mg/kg). Pimozide (D2 antagonist) decreased jumps (2 and 5 mg/kg), and wet dog shakes, burrows, and body weight loss (5 mg/kg). Domperidone (D2 antagonist) decreased jumping and hypothermia (10 mg/kg) but increased body weight loss (10 mg/kg). Flupenthixol (D2 antagonist) decreased wet dog shakes and burrows (0.05 and 0.1 mg/kg), and jumping, body weight loss, and hypothermia (0.1 mg/kg). Sulpride (D2 agonist) (5 mg/kg) increased all symptoms.
Herz et al. (1974)d-Amphetamine (0.5, 1, 2, and 5 mg/kg); cocaine (5, 10, and 25 mg/kg); L-DOPA (100 mg/kg); apomorphine (1, 2.5, and 5 mg/kg); desipramine (2.5, 5, and 10 mg/kg). Administered intraperitoneally.Rat8–16Precipitated, levallorphan (1 mg/kg, i.p.) on day 10Morphine subcutaneous implant (dose NR), six pellets implanted over 10 daysEye twitching, diarrhea, flying, jumping, lacrimation, ptosis, rhinorrhea, salivation, teeth chattering, wet dog shakes, and writhingd-Amphetamine increased jumping (0.5 and 1, 2 mg/kg) and teeth chattering (1 mg/kg), and decreased wet dog shakes (0.5 and 1 mg/kg). All signs decreased at 2 and 5 mg/kg. Cocaine increased jumping (10 mg/kg) and decreased wet dog shakes (10 mg/kg). All signs decreased at 25 mg/kg. L-DOPA (dopamine precursor) decreased ptosis and diarrhea (100 mg/kg) but increased eye twitching (100 mg/kg). Apomorphine (D2 agonist) decreased ptosis and increased eye twitching at 1 mg/kg, increased ptosis and decreased diarrhea at 2.5 mg/kg, and decreased ptosis and diarrhea but increased eye twitching at 5 mg/kg. Desipramine decreased ptosis and diarrhea but increased eye twitching at all doses, and increased jumping at 5, 10, and 20 mg/kg.
  • NR, not reported.