Reversal of prenatal diazepam-induced deficit in a spatial-object learning task by brief, periodic maternal separation in adult rats.
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.
Cannizzaro
E
E
Dipartimento di Scienze Farmacologiche, Università di Palermo, V. Vespro 129, 90127 Palermo, Italy.
Martire
M
M
Gagliano
M
M
Plescia
F
F
La Barbera
M
M
Mantia
G
G
Mineo
A
A
Cannizzaro
G
G
Cannizzaro
C
C
D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D018757:GABA Modulators / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced / Q000534:rehabilitation*; D016014:Linear Models; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
D018757:GABA Modulators; D003975:Diazepam