Altered psychostimulant sensitivity in mice overexpressing epidermal growth factor

Abstract

Epidermal growth factor (EGF) and its structurally related proteins are involved in the developmental regulation of various brain neurons, including midbrain dopaminergic neurons. We have reported that EGF and EGF receptor abnormalities in both the brain tissues and peripheral blood of schizophrenic patients, which might be implicated in dopaminergic dysfunction of this disease. EGF overexpression in transgenic (Tg) mice displayed alterations in physical development, behavioral abnormalities in sensorimotor gating and prepulse inhibition of acoustic startle at the adult stage. In the present study, weinvestigated psychostimulant sensitivity of EGF Tg mice. At the adult stage, mice were challenged with cocaine (20 mg/kg, i.p. for 5days), and locomotor activity was examined (day1, 3, 5). EGF Tg mice enhanced behavioral responses to cocaine. Control mice gradually increased locomotor responses to cocaine during their daily injections, whereas EGF Tg mice required repeated injections and exhibited time delay in cocaine responses. Repeated administration of psychostimulant drugs, such as cocaine was induced behavioral sensitization in EGF Tg mice. In addition, the expression of monoamine transporter in the globus pallidus of EGF Tg mice altered compared to that of control animals. These results suggest that drug addiction might be implicated in dopaminergic neuron as monoamine transporter. Our findings indicate a potential link between EGF receptor activation and drug addiction.