Abstract
Rats with a neonatal ventral hippocampal lesion (NVHL) are used to model schizophrenia. They show enhanced locomotion and difficulties in learning after puberty. Such behavioral modifications are strengthened by dopaminergic psychostimulant drugs, which is also relevant for schizophrenia because illustrating its dopaminergic facet. But it remains questionable that only dopaminergic drugs elicit such effects. The behavioral effects could simply represent a non specific arousal, in which case NVHL rats should also be hyper-responsive to other vigilance enhancing drugs. We administered an adenosine (caffeine) or an adrenaline receptor antagonist, (RX821002) at doses documented to modify alertness of rats, respectively 5 mg/kg and 1 mg/kg. Rats were selected prior to the experiments using magnetic resonance imaging (MRI). Each group contained typical and similar NVHL lesions. They were compared to sham lesioned rats. We evaluated locomotion in a new environment and the capacity to remember a visual or acoustic cue that announced the occurrence of food. Both caffeine and RX82100 enhanced locomotion in the novel environment, particularly in NVHL rats. But, RX82100 had a biphasic effect on locomotion, consisting of an initial reduction preceding the enhancement. It was independent of the lesion. Caffeine did not modify the learning performance of NVHL rats. But, RX821002 was found to facilitate learning. Patients tend to intake much more caffeine than healthy people, which has been interpreted as a means to counter some cognitive deficits. This idea was not validated with the present results. But adrenergic drugs could be helpful for attenuating some of their cognitive deficits.
Highlights
Neonatal lesion of the ventral hippocampus (NVHL) in rats produces an animal model currently used to investigate the developmental hypothesis of schizophrenia
Even if no major damage was found to the ventral hippocampus in most schizophrenic patients, the model is still relevant since it involves developmental changes, especially within the dopaminergic mesocorticolimbic system considered central to the model and to the disease (Halim and Swerdlow, 2000)
The behavioral consequence of the neonatal lesion could consist of a non specific arousal, in which case neonatal ventral hippocampal lesion (NVHL) rats should be hyper-responsive to any vigilance enhancing drug
Summary
Neonatal lesion of the ventral hippocampus (NVHL) in rats produces an animal model currently used to investigate the developmental hypothesis of schizophrenia (reviews in: Lipska, 2004; Tseng et al, 2009). The hypersensitivity to dopaminergic drugs was demonstrated by administering indirect dopaminergic drugs, such as amphetamine or cocaine (Lipska et al, 1993; Chambers and Taylor, 2004; Corda et al, 2006) These drugs, as well as apomorphine a direct DA agonist, enhanced locomotion (Macedo et al, 2008, 2010; François et al, 2009; Bychkov et al, 2011; Sandner et al, 2011, 2012) and elicited behavioral modifications in NVHL rats that had been documented with the set of tests as used in the present study (Macedo et al, 2008, 2010; Sandner et al, 2011, 2012). There is an additional reason for having considered a noradrenergic agent, namely the increasing interest
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