Alteration in the GABAergic network of the prefrontal cortex in a potential animal model of psychosis
Dopamine (DA)-immunoreactivity was investigated in the prefrontal cortex (PFC) of 90 day old adult male gerbils (Meriones unguiculatus) after they had received a single dose of either methamphetamine (50 mg/kg; i.p.) or saline at the age of postnatal day 14. For that purpose, a selective and sensitive antibody directed against glutaraldehyde-conjugated dopamine was applied. All detectable fragments of dopamine-immunoreactive fibres were identified in consecutive frontal sections of the pregenual prefrontal cortex, and their total numbers and total length were determined in the medial (mPFC) and orbital prefrontal cortex (oPFC). The results indicate that a single application of methamphetamine during early postnatal development caused a significant and severe restraint of the subsequent maturation of the prefrontal dopamine-innervation. Although, on postnatal day 14, the total dopamine-immunoreactivity had only attained about 4% (mPFC) and 7% (oPFC) of the regular adult values, this solitary pharmacological challenge entailed final adult innervation densities which were about 38% (mPFC) and 50% (oPFC) below those of the controls. Considering the pivotal role which mesoprefrontal dopaminergic afferents play in morphogenesis and regular functioning, the present results are discussed with current understanding of structural and functional plasticity during maturation of the prefrontal cortex.