A COMPARISON OF THE EFFECTS OF AMPHETAMINE, STRYCHNINE AND CAFFEINE ON PREPULSE INHIBITION AND LATENT INHIBITION

Sensorimotor gating deficits characterize several neuropsychiatric dis orders, including schizophrenia. Prepulse inhibition (PPI) and latent inhibition (LI) are measures that are used to assess sensorimotor gati ng and have been found to be reduced in schizophrenia patients. In PPI , a weak stimulus presented immediately prior to a startling stimulus attenuates the startle response. In LI, pre-exposure to a stimulus ret ards the subsequent association of that stimulus with a consequence (e .g. footshock). In rats, indirect dopamine (DA) agonists such as amphe tamine disrupt both PPI and LI. Amphetamine has also been reported to increase exploratory locomotion at doses that decrease PPI and LI. Suc h behavioral activation might complicate the interpretation of ampheta mine-induced changes in measures of sensorimotor gating. The present s tudy was conducted in order to compare the effects of three behavioral ly activating drugs on PPI, LI and locomotor activity. Separate groups of rats were treated with either vehicle, the DA releaser amphetamine (1.5 mg/kg), the glycine antagonist strychnine (0.75 mg/kg), or the a denosine receptor antagonist caffeine (10 mg/kg) and then tested in ei ther startle chambers (for PPI) or an active avoidance chamber (for LI ). Locomotion was measured by inter-trial crossing in the avoidance ch amber. Amphetamine stimulated locomotion and disrupted both PPI and LI , but did not elevate startle amplitude. In contrast, caffeine increas ed locomotion, but had no effect on PPI or LI. Strychnine did not incr ease locomotion significantly, but did increase startle amplitude and disrupt PPI and LI. Hence, neither increased startle amplitude nor loc omotor activation are necessary or sufficient conditions for disruptio n of sensorimotor gating as measured by PPI and LI.