Effects of GABAergic drugs on brain stimulation reward as assessed by a 'threshold' method

Rats were trained in a two-lever intracranial self-stimulation (ICSS) paradigm. Responses at the first lever delivered brain stimulation which was decreased in magnitude after every 5 responses. Responses at the second re-set the available current to its original value. The current level at which the re-set responses occurred was defined as the 'reward threshold'. The rate of responding at each current level during the stimulate-re-set sequence was also determined. This paradigm, therefore, allowed simultaneous rate-independent and rate-dependent assessment of ICSS. Decreased reward, as demonstrated by an elevated 'reward threshold', was produced in a dose-related manner by the GABA antagonist picrotoxin. Similar effects could be produced by making each stimulation train less rewarding, i.e. by reducing the amount of charge delivered per stimulation. Conversely, increased reward, as indicated by a lower 'reward threshold', was produced in a dose-related manner by the GABA-mimetic muscimol, or by increasing the amount of charge delivered by each stimulation. Response rats were not significantly changed at any stimulation intensity following treatment with either drug. These data suggest that the effects of picrotoxin and muscimol on ICSS are due to changed perception of reward and not to altered performance of the lever pressing task. An important role for GABA in the mediation of reward needs, therefore, to be considered.