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.
Key wordsEarly protein malnutrition Elevated plusmaze Diazepam Non-benzodiazepine anxiolytics 5-HT Rat
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- Broadhurst PL (1960) Applications of biometrical genetics to the inheritance of behaviour. In: Eysenck HJ (ed) Experiments in personality, vol. 1, Psychogenetics and psychopharmacology. Routledge and Kegan Paul, London, pp 1–102Google Scholar
- Critchley MAE, Njung'e K, Handley SL (1988) Prevention of 8-OH-DPAT anxiogenic effect by ipsapirone and by 5-HT1 antagonist beta-adrenoceptor antagonists. Br J Pharmacol Suppl 94:389PGoogle Scholar
- De Oliveira LM (1985) Malnutrition and environment: interaction effects upon animal behavior. Rev Chil Nutr 13:99–108Google Scholar
- Graeff FG (1984) The anti-aversive action of minor tranquillizers. TIPS 5:230–233Google Scholar
- Graeff FG (1990) Brain defense systems and anxiety. In: Roth M, Burrows GD, Noyes R (eds) The neurobiology of anxiety. Elsevier, Amsterdam, pp 307–354Google Scholar
- Traber J, Glaser T (1987) 5-HT1a receptor-related anxiolytics. TIPS 8:432–437Google Scholar
- Waldmeier PC, Williams M, Baumann PA, Bischoff S, Sills MA, Neale RF (1988) Interactions of isamoltane (CGP 361A), an anxiolytic phenoxypropanolamine derivate, with 5-HT1 receptor subtypes in the rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 337:609–620Google Scholar