Comparisons of the densities of NADPHd reactive and nNOS immunopositive neurons in the hippocampus of three age groups of young nonhandled and handled rats

The complete absence of handling of male rats during neonatal development ( from birth to postnatal day 21) correlates with an impairment of latent inh ibition [J. Feldon, I. Weiner, From an animal model of an attentional defic it towards new insights into the pathophysiology of schizophrenia, J. Psych iatr. Res. 26 (1992) 345-366.]. Such nonhandling of rats reportedly also co rrelates with a decreased expression of reduced nicotinamide adenine dinucl eotide phosphate-diaphorase (NADPHd) reactivity in the hippocampus in adult rats (6 months of age) when compared with rats of the same age that were h andled during the same neonatal period [R.R. Vaid, B.K. Yee, U. Shalev, J.N . Rawlins, I. Weiner, J. Feldon, S. Totterdell, Neonatal nonhandling and in utero prenatal stress reduce the density of NADPH-diaphorase-reactive neur ons in the fascia dentata and Ammon's horn of rats, J. Neurosci. 17 (1997) 5599-5609.]. The present study investigated whether such a decrease in NADP Hd activity would be detectable at earlier ages. Therefore, the present stu dy assessed the density of nitric oxide (NO) producing neurons in the fasci a dentata and Ammon's horn in 28-, 54-, and 118-day-old nonhandled and hand led male rats using NADPHd histochemistry and immunohistochemical localizat ion of neuronal isoform of nitric oxide synthase (nNOS), a NADPHd. This sho wed that in these three age groups, the numbers of NADPHd positive neurons per unit area throughout the hippocampus of rats that received no handling during neonatal development did not differ significantly from those of rats that received regular daily handling. In addition, we found in the rats of 118 days of age that the areal density of nNOS immunopositive neurons in t he hippocampus also did not differ significantly between nonhandled and han dled rats. Nevertheless, in a parallel study, rats from the same experiment al group receiving identical treatments showed the expected impairment of l atent inhibition at 4 months of age [R. Weizman, J. Lehmann, S. Leschiner, I. Allmann, T. Stoehr, C. Heidbreder, A. Domeney, J. Feldon, M. Gavish, Lon g-lasting effect of early handling on the peripheral-type benzodiazepine re ceptor, Pharmacol. Biochem. Behav. in press.]. These results suggest that n onhandling of rats during the early neonatal period, that does result in im pairment in latent inhibition, does not affect the numbers of NO producing neurons in the hippocampus in rats of young ages, including the age of obse rved impairment of latent inhibition. (C) 1999 Elsevier Science B.V. All ri ghts reserved.