Effects of 4-aminopyridine on classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response.

A large body of data suggests that potassium channels may play an important role in learning and memory. Previous in-vitro research in a number of species including Hermissenda and the rabbit suggests that a 4-aminopyridine-sensitive transient potassium channel may be involved in classical conditioning. We investigated the effects of in-vivo 4-aminopyridine administration (0.5 mg/kg) on classical conditioning of the rabbit nictitating membrane response using a battery of tests designed to assess the associative, sensory, and motor contributors of 4-aminopyridine to responding. 4-Aminopyridine enhanced both classical conditioning and conditioning-specific reflex modification compared with a saline vehicle control, and these effects had several nonassociative components including an increase in the frequency of responding to both the conditioned and the unconditioned stimuli, suggesting a sensitizing effect of the drug. Although 4-aminopyridine can have peripheral effects, it may also modify cerebellar excitability or hippocampal neurotransmitter balance resulting in heightened responsiveness to stimulation.