Sensitized Attentional Performance and Fos-Immunoreactive Cholinergic Neurons in the Basal Forebrain of Amphetamine-Pretreated Rats

Background The consequences of repeated exposure to psychostimulants have been hypothesized to model aspects of schizophrenia. This experiment assessed the consequences of the administration of an escalating dosing regimen of amphetamine (AMPH) on attentional performance. Fos-like immunoreactivity (Fos-IR) in selected regions of these rats’ brains was examined to test the hypothesis that AMPH-sensitized attentional impairments are associated with increased recruitment of basal forebrain cholinergic neurons. Methods Rats were trained in a sustained attention task and then treated with saline or in accordance with an escalating dosing regimen of AMPH (1–10 mg/kg). Performance was assessed during the pretreatment and withdrawal periods and following the subsequent administration of AMPH “challenges” (.5, 1.0 mg/kg). Brain sections were double-immunostained to visualize Fos-IR and cholinergic neurons. Results Compared with the acute effects of AMPH, AMPH “challenges,” administered over 2 months after the pretreatment was initiated, resulted in significant impairments in attentional performance. In AMPH-pretreated and -challenged animals, an increased number of Fos-IR neurons was observed in the basal forebrain. The majority of these neurons were cholinergic. Conclusions The evidence supports the hypothesis that abnormally regulated cortical cholinergic inputs represent an integral component of neuronal models of the attentional dysfunctions of schizophrenia.