Pleiotrophin gene transcription in the rat nucleus accumbens is stimulated by an acute dose of amphetamine

Pleiotrophin (PTN) is a heparin-binding protein with diverse functions. For example, it stimulates neurite outgrowth, mitogenesis, repair and differentiation, effects that are similar to those of the neurotrophins. The neurotrophins have, in recent years, been implicated as mediators of structural plasticity, suggested to underlie the development of behavioural sensitisation to many drugs of abuse. Since NMDA receptor antagonists inhibit the underlying morphological changes, the mechanisms are thought to be highly dependent on the activation of the NMDA subtype of glutamate receptors. To investigate if PTN has a possible role in structural plasticity, its responsiveness to an acute dose of amphetamine was studied. Amphetamine is a well-characterised inducer of sensitisation. A group of rats was systemically treated with amphetamine (10 mg/kg) and the effect on the PTN gene transcription was studied 4 h later. A separate group of rats was pretreated with the NMDA receptor antagonist MK-801 (0.25 mg/kg) 30 min prior to the administration of amphetamine. Northern blot analysis revealed a significant increase of the PTN transcript after the administration of amphetamine. However, MK-801 pretreatment did not block this effect; in contrast, it further increased PTN mRNA levels. As the response to the two drugs resembles the one earlier reported on the gene expression of brain-derived neurotrophic factor (BDNF), the present results suggest that PTN may be an attractive protein to study further in the field of synaptic plasticity.