PMID- 15922060 OWN - NLM STAT- MEDLINE DCOM- 20050802 LR - 20191210 IS - 0166-4328 (Print) IS - 0166-4328 (Linking) VI - 161 IP - 2 DP - 2005 Jun 20 TI - Reversal of prenatal diazepam-induced deficit in a spatial-object learning task by brief, periodic maternal separation in adult rats. PG - 320-30 AB - In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learning performance was examined employing a non-aversive spatial, visual and/or tactile task, the "Can test". Behavioural reactivity, emotional state and fear/anxiety-driven behaviour were also examined using open field (OF), acoustic startle reflex (ASR) and elevated plus-maze (EPM) tests. A single daily injection of DZ (1.5mg/kg, s.c.), over gestational days (GD) 14-20, induced, in an age-independent manner, a severe deficit in learning performance, a decrease in locomotor and explorative activity and an increase in peak amplitude in the ASR. Furthermore, anxiety-driven behaviour in EPM was disrupted. Daily maternal separation for 15 min over postnatal days 2-21 exerted opposite effects in all the paradigms examined. Prenatally DZ-exposed maternal separated rats, in contrast to respective non-separated rats, showed an improvement in learning performance, a decrease in emotionality and a normalization of the exploratory behaviour in EPM. These results suggest that a greater maternal care, induced by separation, can serve as a source for the developing brain to enhance neuronal plasticity and to prevent the behavioural abnormalities induced by prenatal DZ exposure. FAU - Cannizzaro, E AU - Cannizzaro E AD - Dipartimento di Scienze Farmacologiche, Universita di Palermo, V. Vespro 129, 90127 Palermo, Italy. FAU - Martire, M AU - Martire M FAU - Gagliano, M AU - Gagliano M FAU - Plescia, F AU - Plescia F FAU - La Barbera, M AU - La Barbera M FAU - Mantia, G AU - Mantia G FAU - Mineo, A AU - Mineo A FAU - Cannizzaro, G AU - Cannizzaro G FAU - Cannizzaro, C AU - Cannizzaro C LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050317 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (GABA Modulators) RN - Q3JTX2Q7TU (Diazepam) SB - IM MH - Acoustic Stimulation/methods MH - Age Factors MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Behavior, Animal/drug effects/physiology MH - Diazepam/*toxicity MH - Exploratory Behavior/drug effects/physiology MH - Female MH - GABA Modulators/*toxicity MH - Learning Disabilities/chemically induced/*rehabilitation MH - Linear Models MH - Male MH - *Maternal Deprivation MH - Maze Learning/drug effects/physiology MH - Motor Activity/drug effects/physiology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Rats, Wistar MH - Reflex, Startle/drug effects/physiology MH - Spatial Behavior/*drug effects/physiology EDAT- 2005/06/01 09:00 MHDA- 2005/08/03 09:00 CRDT- 2005/06/01 09:00 PHST- 2004/07/07 00:00 [received] PHST- 2005/02/21 00:00 [revised] PHST- 2005/02/21 00:00 [accepted] PHST- 2005/06/01 09:00 [pubmed] PHST- 2005/08/03 09:00 [medline] PHST- 2005/06/01 09:00 [entrez] AID - S0166-4328(05)00069-0 [pii] AID - 10.1016/j.bbr.2005.02.022 [doi] PST - ppublish SO - Behav Brain Res. 2005 Jun 20;161(2):320-30. doi: 10.1016/j.bbr.2005.02.022. Epub 2005 Mar 17.