It is well established that epigenetic factors influence the maturation of neurotransmitter systems. Social isolation as well as an early intervention with methamphetamine (MA) lead to a diminished maturation of dopaminergic (DA) fibres in cortical and striatal areas in the brain of Mongolian gerbils. The aim of this study was to prove whether isolated rearing (IR) and the application of a single dose of MA on postnatal day 14 affect the maturation of DA fibres in caudal limbic areas. Therefore the DA fibre densities were quantified in the dorsolateral and ventrolateral entorhinal cortex (EC), the ventral subiculum (SUB) and in three amygdala nuclei - the basolateral (BLA), the lateral (LA) and the central (CA) nucleus. Our results showed that IR and an early MA application led to an increase of DA fibre densities in various caudal limbic areas. Whereas the BLA was affected by both IR and MA, the LA and the medial left CA were only influenced by MA in IR animals. The DA fibre surplus in the ventrolateral EC was significant in MA treated ER and IR animals in the left and right hemisphere, respectively. The SUB and the dorsolateral EC remained unaffected by both epigenetic factors. Altogether, the BLA seems to be the area which responds most sensitively to IR and MA. Previous studies in our laboratory showed a suppressive maturation of DA fibres in the prefrontal cortex (PFC) and nucleus accumbens (NAC) induced by the same set of epigenetic factors. Thus, due to the close functional connection between the PFC and limbic areas, it could be assumed that the suppressive maturation of prefrontal DA fibres implicates an enhancement of DA innervation densities in caudal limbic areas. Imbalances in the morphology and physiology of the different DA projections are suggested here to be crucial in the aetiology of schizophrenia.

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The current study investigated the influence of impoverished rearing (IR) conditions and a single early methamphetamine challenge (MA; 50 mg/kg i.p.) on day 14 on the postnatal maturation of acetylcholinesterase-positive (AChE+) fibres in the hippocampal dentate gyrus (DG) of gerbils (Meriones unguiculatus). The layer-specific densities of histochemically stained AChE+ fibres were quantified in two planes of the left and right DG in young adults (day 90). Compared to enriched reared (ER) animals, the AChE+ fibre densities turned out to be higher in both the septal and the temporal plane of both hemispheres in saline treated IR and MA treated ER gerbils. The temporal plane was slightly more affected than the septal plane. In IR animals, MA treatment selectively diminished the AChE+ fibre densities in the subgranular layer of both left and right temporal DG. In conclusion, the maturation of AChE+ fibres is vulnerable to both rearing conditions and early MA challenge. The results correlate with our previous studies on the dentate cell proliferation rates and the serotonergic innervation, two parameters which are similarly affected by the experimental design. Thus, disturbances of the ACh system may impair the hippocampal plasticity and hippocampus-related cognitive and emotional function.