Early life protein malnutrition changes exploration of the elevated plus-maze and reactivity to anxiolytics.
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.
Almeida
S S
SS
Laboratory of Psychobiology, FFCLRP, University of São Paulo, Riberião Preto, Brazil.
de Oliveira
L M
LM
Graeff
F G
FG
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011502:Protein-Energy Malnutrition / Q000523:psychology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016713:Ritanserin
D014151:Anti-Anxiety Agents; D010880:Piperidines; D011412:Propanolamines; D011743:Pyrimidines; D016713:Ritanserin; C043077:ipsapirone; C058392:isamoltane; D003975:Diazepam