Advertisement

Psychopharmacology

, Volume 103, Issue 4, pp 513–518 | Cite as

Early life protein malnutrition changes exploration of the elevated plus-maze and reactivity to anxiolytics

  • S. S. Almeida
  • L. M. de Oliveira
  • F. G. Graeff
Original Investigations

Abstract

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 words

Early protein malnutrition Elevated plusmaze Diazepam Non-benzodiazepine anxiolytics 5-HT Rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Almeida SS, De Oliveira LM, Bichuette MZ, Graeff FG (1988) Early malnutrition alters the effect of chlordiazepoxide on inhibitory avoidance. Braz J Med Biol Res 21:1033–1036PubMedGoogle Scholar
  2. Almeida SS, De Oliveira LM, Graeff FG (1990) Decreased reactivity to anxiolytics caused by early protein malnutrition in rats. Pharmacol Biochem Behav 36:997–1000CrossRefPubMedGoogle Scholar
  3. Barnes RH, Neely CS, Kwong E, Labadan BA, Frankova S (1968) Postnatal nutritional deprivations as determinants of adult rat behavior toward food, its consumption and utilization. J Nutr 96:467–476PubMedGoogle Scholar
  4. Brioni JD, Orsingher OA (1988) Operant behavior and reactivity to the anticonflict effect of diazepam in perinatally under-nourished rats. Physiol Behav 44:193–198CrossRefPubMedGoogle Scholar
  5. 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
  6. Commissaris RL, Harrington GM, Altman HJ (1990) Benzodiazepine anti-conflict effects in Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rats. Psychopharmacology 100:287–292PubMedGoogle Scholar
  7. Critchley MAE, Handley SL (1987) Effects in the X-maze anxiety model of agents acting at 5HT1 and 5-HT2 receptors. Psychopharmacology 93:502–506CrossRefPubMedGoogle Scholar
  8. 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
  9. De Oliveira LM (1985) Malnutrition and environment: interaction effects upon animal behavior. Rev Chil Nutr 13:99–108Google Scholar
  10. Durel LA, Krantz DS, Barrett JE (1986) The antianxiety effect of beta-blockers on punished responding. Pharmacol Biochem Behav 25:371–374CrossRefPubMedGoogle Scholar
  11. Falk JL, Burnidge GK (1970) Fluid intake and punishment-attenuating drugs. Physiol Behav 5:199–202PubMedGoogle Scholar
  12. File SE (1990) One-trial tolerance to the anxiolytic effects of chlordiazepoxide in the plus-maze. Psychopharmacology 100:281–282CrossRefPubMedGoogle Scholar
  13. Frankova S, Barnes RH (1968) Effect of malnutrition in early life on avoidance conditioning and behavior of adult rats. J Nutr 96:485–493PubMedGoogle Scholar
  14. Goa KL, Ward A (1986) Buspirone: a preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs 32:114–129PubMedGoogle Scholar
  15. Graeff FG (1984) The anti-aversive action of minor tranquillizers. TIPS 5:230–233Google Scholar
  16. 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
  17. Handley SL, Mithani S (1984) Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of “fear”-motivated behavior. Naunyn-Schmiedeberg's Arch Pharmacol 327:1–5CrossRefGoogle Scholar
  18. Hernández JR, Manjarréz GG, Chagoya G (1989) Newborn humans and rats malnourished in utero: free plasmaL-tryptophan, neutral amino acids and brain serotonin syntesis. Brain Res 488:1–13CrossRefPubMedGoogle Scholar
  19. Hoyer D (1988) Molecular pharmacology and biology of 5-HT1c receptors. TIPS 9:89–94PubMedGoogle Scholar
  20. Levitsky DA, Barnes RH (1970) Effect of early malnutrition on the reaction of adult rats to aversive stimuli. Nature 225:468–469CrossRefPubMedGoogle Scholar
  21. Leysen JE, Gommeren W, Van Gompell P, Wynantes J, Janssen PFM, Laudron PM (1985) Receptor binding properties in vitro and in vivo of ritanserin: a very potent and long acting serotonin-S2 antagonist. Mol Pharmacol 27:600–611PubMedGoogle Scholar
  22. Lynch A (1976) Passive avoidance behavior and response thresholds in adult male rats after early postnatal undernutrition. Physiol Behav 16:27–32CrossRefPubMedGoogle Scholar
  23. Morgane P, Miller M, Kemper T, Stern W, Forbes W, Hall R, Bronzino J, Kissane J, Hawrylewicz E, Resnick O (1978) The effects of protein malnutrition on the developing central nervous system in the rat. Neurosci Biobehav Rev 2:137–230CrossRefGoogle Scholar
  24. Moser PC (1989) An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone. Psychopharmacology 99:48–53CrossRefPubMedGoogle Scholar
  25. Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529CrossRefPubMedGoogle Scholar
  26. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167CrossRefPubMedGoogle Scholar
  27. Rajalakshmi R, Parameswaran M, Ramakrishnan CV (1974) Effects of different levels of dietary protein on brain glutamate dehydrogenase and decarboxilase in young albino rats. J Neurochem 23:123–127PubMedGoogle Scholar
  28. Resnick O, Morgane PJ (1984) Ontogeny of the levels of serotonin in various parts of the brain in severely protein malnourished rats. Brain Res 303:163–170CrossRefPubMedGoogle Scholar
  29. Salmon P, Gray JA (1986) Effects of propranolol on conditioned suppression, discriminated punishment and discriminated non-reward in the rat. Psychopharmacology 88:252–257CrossRefPubMedGoogle Scholar
  30. Smart JL, Whatson TS, Dobbing J (1975) Thresholds of response to electric shock in previously undernourished rats. Br J Nutr 34:511–516PubMedGoogle Scholar
  31. Söderpalm B, Hjoth S, Engel JA (1989) Effects of 5-HT1a receptor agonists andL-5-HTP in Montgomery's conflict test. Pharmacol Biochem Behav 32:259–265CrossRefPubMedGoogle Scholar
  32. Traber J, Glaser T (1987) 5-HT1a receptor-related anxiolytics. TIPS 8:432–437Google Scholar
  33. 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
  34. Wiggins R, Fuller G, Enna S (1984) Undernutrition and the development of brain neurotransmitter systems. LIfe Sci 35:2085–2094CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • S. S. Almeida
    • 1
  • L. M. de Oliveira
    • 1
  • F. G. Graeff
    • 1
  1. 1.Laboratory of PsychobiologyFFCLRP, Campus of the University of São PauloRibeirão Preto, SPBrazil

Personalised recommendations