Bipolar disorder, characterised by extreme cyclical variations in mood between depression and mania, is a common, debilitating and sometimes fatal psychiatric condition with an unclear aetiology. In this paper we propose a hypothesis for the development of bipolar disorder through which neuroplastic changes in response to an index depressive episode leads to the amplification of subthreshold pleasurable stimuli that then drive conversion into a manic state. This ‘pleasure deafferentation hypothesis’ is reached through a discussion of the neuroscientific basis of deafferentation at the level of the neuron and its role in the development of various neurological and psychiatric phenomena before a case for deafferentation as applied to bipolar disorder is justified and its implications discussed.