Changes in astrocytic basic fibroblast growth factor expression during andafter prolonged exposure to escalating doses of amphetamine

We have shown that brief exposure to amphetamine leads to sustained glutama te-dependent increases in expression of the neurotrophic, neuroprotective f actor, basic fibroblast growth factor, in astrocytes in dopaminergic cell b ody regions and that blockade of basic fibroblast growth factor in this reg ion prevents the development of behavioral sensitization to amphetamine. He re we examine the effects of prolonged exposure to an escalating-dose regim en of amphetamine known to induce long-lasting sensitization to amphetamine and leading to increases in neuronal dendritic length and spine density in nucleus accumbens and prefrontal cortex and to decreases in spine density in occipital cortex. Astrocytic basic fibroblast growth factor immunoreacti vity was increased in both dopaminergic cell body and terminal regions one week after termination of a two-week amphetamine treatment (1-4 mg/kg). The se effects were not evident one week after a five-week treatment (1-9 mg/kg ) and, in fact, one month later basic fibroblast growth factor levels in ce ll body regions were decreased. In the occipital cortex, basic fibroblast g rowth factor immunoreactivity was decreased one week after the two-week amp hetamine treatment, but was not different from that seen in saline-treated animals after the five-week treatment. Increased astrocytic basic fibroblas t growth factor expression appears to be an early, but relatively prolonged , response to amphetamine exposure and seems to parallel structural changes induced by repeated drug exposure. These findings suggest that basic fibroblast growth factor may participate in the development of structural changes brought about by amphetamine. The fact that the basic fibroblast growth factor response is not maintained aft er prolonged intense exposure to amphetamine suggests that the factors that initially induce basic fibroblast growth factor expression are self-regula ting. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved .