European Neuropsychopharmacology 13 (2003) 209–217 www.elsevier.com / locate / euroneuro Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to reveal 5-HT1A receptor function a, c a a a b * C. Cannizzaro , M. Martire , E. Cannizzaro , R. Monastero , M. Gagliano , A. Mineo , G. Provenzano a Department of Pharmacological Sciences, University of Palermo, Policlinico ‘ P . Giaccone’, V . Vespro 129, 90127 Palermo, Italy b Department of Statistical and Mathematical Sciences, University of Palermo, Palermo, Italy c Department of Pharmacology, Catholic University of Sacred Heart, Roma, Rome, Italy Accepted 5 November 2002 Abstract Central GABAergic and serotoninergic systems interact with one another and are implicated in controlling different behaviours. A gentle early long-lasting handling can prevent the deficits in locomotion and exploration in open field (O.F.) in 3-month-old male rats prenatally exposed to diazepam (DZ). Purpose of this study was to extend the research to older handled rats prenatally exposed to DZ and to assess the activity of 5-HT1A receptors (Rs), evaluating the performance in O.F. at 3 and 18 months of age following 8-OH-DPAT administration. A single daily s.c. injection of DZ (1.5 mg / kg) from gestation day 14 to gestation day 20 induced in aged, but not in young rats, a decrease in total distance travelled (TDT) and in rearing frequency (RF) and an increase of transitions from the periphery to the centre of the arena (CNT) and in the time spent in the centre of the arena (CAT), compared to controls. 8-OH-DPAT (0.150 mg / kg s.c.), given 1 h before testing, increased TDT and decreased RF, CNT and CAT in both vehicle- and DZ-exposed young rats. In aged rats prenatally exposed to DZ, 8-OH-DPAT induced an increase in TDT and a slight decrease in RF, CNT and CAT. These findings indicate that the effects of handling and of 8-OH-DPAT in prenatally DZ-exposed rats are age-dependent and suggest that O.F. test can represent a valid tool to identify the changes in 5-HT1A Rs activity following drug treatment.  2003 Elsevier Science B.V./ECNP All rights reserved. Keywords: Rats; Prenatal diazepam; Long-lasting handling; Aging; 8-OH-DPAT; Open field test 1. Introduction inhibition of GABA / BDZ Rs (Lima et al., 1995; Siniscal- chi et al., 2001). Central GABAergic and serotoninergic systems interact Several aspects of the functioning of GABAergic and with one another and are implicated in the control of serotoninergic systems can be affected by environmental ¨ different behaviours (Lanfumey et al., 1997; Soderpalm et stimuli (Biggio et al., 1990; File et al., 1990). One of the al., 1997; Kelly et al., 1999; Kishimoto et al., 2000). most employed tools of early environmental manipulations GABAergic system is reported to modulate serotoninergic on the animals is handling. In rats, a repeated gentle activity; indeed, the activation of GABA / benzodiazepine handling results in an increased response of GABA / BDZ (BDZ) receptors (Rs) exerts antagonistic effects on Rs and in a reduction of 5-HT function in the brain serotoninergic neurotransmission (Nakamura and (Biggio et al., 1981, 1990; File et al., 1990). Handled rats, Fukushima, 1977; Rastogi et al., 1978; Laurent et al., when exposed to behavioural testing, are less anxious and 1983), while opposite consequences are produced by exhibit an attenuated reactivity compared to non-handled animals (Andrews and File, 1993; Kelley, 1993; Caldji et al., 2000). Moreover, handling procedure during infancy *Corresponding author. Tel.: 139-91-655-3259; fax: 139-91-655- induces biochemical and behavioural long-term changes, 3212. E-mail address: psycho@unipa.it (C. Cannizzaro). which are able to attenuate the impairment in motor 0924-977X / 03 / $ – see front matter  2003 Elsevier Science B.V./ECNP All rights reserved. doi:10.1016 / S0924-977X(03)00012-9