Some science behind the scenes

Prepulse inhibition

One of the strange  side effects of the opioids is ‘Prepulse inhibition’ (PPI) deficit or the  inhibition of PPI.   

Prepulse Inhibition (PPI) is a neurological phenomenon in which some light initial stimulus – such as a sound or a gentle touch  - has the effect of adapting the nervous system so that any much stronger signal which comes afterwards is toned down – we are not as startled by it.  It is there so that if the body is warned by a weak signal, it gets ready for a response, but isn’t incapacitated by anything bigger that comes along. The flight or fight response is thus more effective.

‘The reduction of the amplitude of startle’ as scientists call it affects not only the 5 senses, so that any really startling subsequent noise or touch or taste etc doesn’t shock, but it also affects our muscles.  So we don’t ‘jump out of our skin’!

 Deficits of prepulse inhibition manifest in the inability of the person or animal to tone down repeated stimuli -  in the end all stimuli are treated equally.  There may be a sort of sensory bombardment - hyper sensitivity. We become super aware of everything going on, absolutely everything – sounds, taste, touch, smells, sights.

PPI inhibition [PPII] is a direct side effect of excess dopamine release and excess dopamine has been linked with schizophrenia.  And indeed schizophrenics suffer from PPI deficit.  It is clear, however, that a whole series of disorders of the brain – ADHD, Tourette’s, Alzheimer’s, temporal lobe epilepsy – result in PPI deficits.

At one time it was thought that Papaverine helped to reduce these effects, but when scientists produced  PPI deficits using  apomorphine,   Papaverine failed to reverse these  induced PPI deficits at all doses,  pretreatment times, and prepulse intervals.