Age- and region-dependent alterations in the GABAergic innervation in the brain of rats treated with amphetamine

Mechanisms underlying the pathogenesis of psychotic disorders were explored by monitoring the expression of GABAergic neurons in an animal model. Male rats of postnatal days 21 and 60 were intraperitoneally injected with amphetamine (Amph), 5 mg/kg, or saline three times daily for 6 d. After 1-d or 14-d withdrawal from Amph, they were challenged on day 8 (W1d) or on day 21 (W14d) with a single same dosage and then perfused. Immunostaining on the brain sections using an anti-glutamic acid decarboxylase (GAD67) antiserum revealed that the Amph treatment increased the densities of the GAD67-immunoreactive boutons by approx. 36 to 79% above controls in the layers of motor and somatosensory cortices of the W1d juvenile, whereas for those of W14d, the densities resembled controls. For the Amph-treated adults of both W1d and W14d, the GAD67 immunoreactivity increased 56–133% in these layers. In the striatum, the GAD67 densities responded to Amph in a similar manner to the neocortices. However, for the nucleus accumbens, the GAD67 terminals were up-regulated by 22–64% in all Amph-injected rats of both ages. In the hippocampal CA1–CA3 region of the Amph-administered juvenile, increases of 24–27% of GAD67 terminals occurred for W1d and W14d animals. By contrast, however, in the W1d Amph-injected adult, there were increases of 42–48% in CA1–CA3, at W14d the GAD67 boutons resembled controls or were reduced. An age-dependent correlation was implicated between behavioural and immunostaining observations. The data support the view that inhibitory regulation is involved in neuronal responses to chronic psychostimulant administration and reflect differential neuronal plasticity among the developing and adult brain regions.