piperidines and Protein-Energy-Malnutrition

In order to investigate whether protein malnutrition in early life causes lasting changes in reactivity to anxiolytic drugs, exploration of the elevated plus-maze was used. Rat dams during lactation (21 days) and pups after weaning until day 49 of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats). From day 50 on all animals ate the same balanced diet. Experiments started on day 70. Under the non-drug condition, M rats tended to explore the open arms of the maze relatively more than W rats. Diazepam (0.5-5 mg/kg, IP) dose-dependently increased the percentage of open/total arm entries without significantly affecting the total number of arm entries in W rats. This selective anxiolytic effect of diazepam was considerably smaller in M rats. Ipsapirone (0.5-5 mg/kg) caused a similar though less pronounced anxiolytic effect in W rats, whereas the drug decreased both the % open/total and total arm entries in M rats. In contrast, ritanserin (0.05-1 mg/kg) significantly increased the % open/total arm entries in M rats only, though not in a dose-dependent way. Isamoltane (2.5-20 mg/kg) was ineffective on both M and W rats. These results indicate that early protein malnutrition causes long-lasting alterations in brain systems regulating emotional behaviour.

Topics: Animals; Anti-Anxiety Agents; Anxiety; Diazepam; Dose-Response Relationship, Drug; Exploratory Behavior; Male; Piperidines; Propanolamines; Protein-Energy Malnutrition; Pyrimidines; Rats; Rats, Inbred Strains; Ritanserin

In order to investigate whether early malnutrition causes lasting changes in the reactivity to anxiolytic drugs, rat dams during lactation (21 days) and pups after weaning until the 49th day of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats). From day 50 on all animals ate the same balanced diet. Experiments started on the 91st day. Rats deprived for 22 hours drank water containing either 1.8% or 2.7% sodium chloride for 30 min in a test chamber, total intake being measured. Dose-effect curves for diazepam (0.5-5.0 mg/kg, IP), as well as for the nonbenzodiazepine anxiolytics ipsapirone (0.5-5.0 mg/kg), ritanserin (0.05-1.0 mg/kg) and isamoltane (2.5-20.0 mg/kg) were determined in M as well as in W rats. Diazepam and ipsapirone dose-dependently released drinking suppressed by either salt concentration in W rats, but caused little or no effect in M rats. Ritanserin and isamoltane were ineffective in both groups. These and previously reported results show that early protein malnutrition markedly reduces anticonflict effects of anxiolytics, indicating long-lasting impairment of neuronal systems underlying emotional behavior.

Topics: Animals; Anti-Anxiety Agents; Body Weight; Diazepam; Diet; Dose-Response Relationship, Drug; Hypertonic Solutions; Lactation; Male; Piperidines; Propanolamines; Protein-Energy Malnutrition; Pyrimidines; Rats; Rats, Inbred Strains; Ritanserin