strychnine and Morphine-Dependence

An investigation was made of the effect of morphine dependence on the characteristics of seizures induced in mice by convulsant drugs with differing mechanisms of action. Morphine dependence was induced in 90-day-old mice (weighing 29 to 32 g) by a 6-day schedule of twice daily i.p. injections of increasing doses of morphine (5, 32.5, 58, 82.5, 100, and 135 mg kg-1). Thirty minutes after the last morphine administration, convulsant drugs (4-aminopyridine 8 mg kg-1, pentylenetetrazol 50 mg kg-1, bicuculline 2.5 mg kg-1, strychnine 2.0 mg kg-1, and beta-mercaptopropionic acid 50 mg kg-1) were injected. 4-Aminopyridine (4-AP) and pentylenetetrazol (PTZ) increased both the number of animals with convulsions and death and in the case of 4-AP the period of convulsion latency was also increased. Naloxone at 1.0 mg kg-1 blocked the 4-AP effects, indicating that this action was mediated through an opioid receptor. Strychnine and beta-mercaptopropionic acid had an effect opposite 4-AP and PTZ in the number of animals with convulsions and death. On the other hand bicuculline had an effect more like 4-AP and PTZ than other inhibitory synapse-blocking drugs. We conclude that chronic morphine treatment modified the response of convulsant drugs depending on their mechanisms of action.

Topics: 3-Mercaptopropionic Acid; 4-Aminopyridine; Aminopyridines; Animals; Bicuculline; Brain; Convulsants; Humans; Mice; Morphine Dependence; Pentylenetetrazole; Receptors, Opioid; Seizures; Strychnine

Single doses of serine (250 mg/kg i.p.) failed to elevate central glycine in mice (1 h after injection), or to compensate for losses caused by implantation of morphine base (70 mg/animal), and reduced the jumping response to nalorphine (100 mg/kg i.p.). In contrast, sustained treatment with 250-mg/kg doses of serine at 24-hour intervals produced increases in brain and medullar glycine (1 h after 4th injection: 46-50% in normal, 39-75% in morphine-dependent mice, and enhanced the jumping response (40% over controls).

Topics: Animals; Brain; Drug Tolerance; Glycine; Humans; Male; Mice; Morphine Dependence; Nalorphine; Serine; Strychnine; Substance Withdrawal Syndrome