Pharmacological analysis of acute morphine dependence in infant rats: close molecular relationship of head-shaking precipitated by opiate antagonists and cholinergic neurotransmission

The influence of drugs affecting different neurotransmitter systems on an acute abstinence heanshaking (AHS) model induced by nalorphine or naloxone was studied in 9-day-old rat pups pretreated (3 h before) with morphine (10mg/kg, i.p.). One hour after the injection of nalorphine (10 mg/kg, i.p.) AHS was stopped by a second dose of morphine (10 mg/kg, i.p.) and reinitiated 1 h later by a higher dose of nalorphine (20 mg/kg, i.p.). In other groups AHS was blocked by spiroperidol (0.1 mg/kg, i.p.), clonidine (0.01 mg/kg, i.p.) or scopolamine (50 mg/kg, i.p.). In these groups a second injection of nalorphine did not reinitiate AHS. In dose-effect curve experiments the AHS induced by naloxone or nalorphine was significantly reduced by previous injections of scopolamine, spiroperidol, metergoline or phentolamine in the corresponding groups. Scopolamine was the only antagonist which displaced the AHS dose-effect curves to the right without affecting the maximal response. Since no common receptors exist for a direct competitive interaction between opiate antagonists and scopolamine, these experiments suggest that a direct molecular relationship exists between the tissue concentration of nalorphine (or naloxone) and the endogenous ACh release during abstinence. Thus, the AHS model in 9-day-old rats clearly differentiates specific from non-specific blockade of the abstinence syndrome, and confirms a distinct or primary role of cholinergic neurotransmission in morphine abstinence

Effect of the neonatal steroid hormone treatment of rats on adult hormone levels and the reactivity of seminal vesicles to parasympathomimetic drugs

Seminal vesicle reactivity to cholinergic agents, plasma testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) conmcentrations and seminal vesicle testosterone concentrations were determined in adult male rats treated during the first 6 h of life with 1.0 ml peanut oil (oil-treated), 1.0 mg testosterone propionate (TP-treated) or 1.2 mg 19-nor-testosterone homofarnesate (19-NT-treated). At 90-100 days of age, the neonatally treated animals presented atrophied accessory genital organsand increased (TP-treated, N=10) or unchanged (19-NT-treated, N=11) pD, values for acetylcholine (vehicle; 5.18 ñ 0.06, N=10; TP-treated; 5.26 ñ 0.06, N+10; 19-NT-treated; 5.14 ñ 0.09, , N=11), and acetyyl-beta-methylcholine (vehicle: 5.19 ñ 0.07; TP-treated: 5.43 ñ 0.06; 19-NT-treated 5.25 ñ 0.07). The relative intrinsic activity, alpha, of acetyl-beta-methylcholine increased after both hormonal treatments (vehicle: 0.85 ñ 0.03; TP-treated:0.95 ñ 0.02; 19-NT-treated: 0.92 ñ 0.03). No variation in mean adult plasma testosterone concentration was observed after neonatal treatmentwith either TP or 19-NT (vehicle:752.93 ñ 273.66, N+8; TP-treated; 459.05 ñ 88.32, N=8; 19-NT-treated: 836.86 ñ 113.08, N=7). However, testosterone content of seminal vesicles of adult rats was decreased in the animalstreated with TP (N=5) and 19-NT (N=6) compared to controls. These results indicate a specific effect of neonatal hormone treatment on androgen metabolism which is demonstrable in the adult