Unmasking latent inhibition in humans.

Presentations of a to-be-conditioned stimulus (CS) on its own impairs subsequent learning when that CS is paired with an unconditioned stimulus (US). Evidence for this latent inhibition (LI) effect in humans is said to require a "masking task" that diverts attention from the CS during preexposure. We present three experiments that demonstrate LI in humans without masking. Subjects performed a computerised task, making speeded responses to an imperative cue (the US) presented within a continuous stream of stimuli. During preexposure, a to-be-CS was presented 20 times among other stimuli, but excluding the US. Instructions ensured subjects actively monitored all stimuli at this time. This was immediately followed by the training phase, which included the US, the preexposed CS, and a novel CS. Both CSs were reliably followed by the US, but these associations were incidental to the instructed task. Nonetheless, some subjects learned the CS-US associations, responding faster when the US followed a CS than when it was unsignalled. All three experiments also found evidence for LI, in that subjects learned the novel CS-US association sooner than the preexposed CS-US association. We conclude that humans can show LI even when actively attending to the CS during preexposure.

Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments in rats.

Chemotherapy can cause serious neurotoxic side effects, such as painful peripheral neuropathies and disabling cognitive impairments. Four experiments examined whether Ibudilast, a clinically approved neuroimmune therapy, would reduce tactile allodynia and memory impairments caused by oxaliplatin in laboratory rats. Rats received an intraperitoneal injection of oxaliplatin (6mg/kg i.p.) or vehicle and were assessed for tactile allodynia 3 or 5days after injection, memory impairments in the novel object and novel location recognition tests 10-12days after injection, and fear conditioning 14days after injection. Ibudilast (7.5mg/kg) or vehicle was administered prior to oxaliplatin (Experiments 1 and 3) or prior to behavioural testing (Experiments 2 and 4). Ibudilast treatment prior to oxaliplatin prevented the development of tactile allodynia and memory impairments. Ibudilast treatment prior to behavioural testing reduced oxaliplatin-induced tactile allodynia, memory impairments, and impaired renewal of fear conditioning. These results suggest that Ibudilast could be an effective treatment against oxaliplatin-induced neuropathies and cognitive impairments.