Dopaminergic agonistic and antagonistic drugs in the ventral tegmentum of rats inhibit and facilitate changes of food-search behaviour

Introduction: The proposal that an increase of dopaminergic (DA) activity in the mesocorticolimbic pathway with an origin in the ventral tegmental area (VTA A10) increases the probability of behavioural change was tested (Koob et al., 1978 - see also Oades, 1985 on the switching role of DA) Methods: Food-deprived animals searched for food pellets placed consistently in 4 holes of a 16-hole-board. They were presented with 9 sessions of 10 trials/session. Groups of rats received lesions of the VTA or injections of the DA D2 antagonist spiroperidol (2µg/0.5 µl) or the DA agonist apomorphine (2 µg(0.5µl) into the VTA before sessions 4 and 7. [Neuroleptic treatment should block local inhibition via autoreceptors and thus lead to increased DA activity in the terminal regions] Results: 1/ Compared to vehicle- or apomorphine-treatment, spiroperidol increased the number of empty hole-visits (errors) 2/ Comparison animals (vehicle- and apomorphine treated) developed individually specific but consistent sequences of hole-visits ("strategy") -- these were disrupted on sessions 4 and 7 after neuroleptic treatment and following VTA damage. (i.e. there was much intra-session switching between sequences from trial to trial.) 3/ Further the identity of the preferred sequence on session 7 was more often different than on session 4 for lesioned and neuroleptic treated animals than for the comparison groups. (i.e there was also inter-session switching between sequences between sessions 4 and 7.) 4/ Although many apomorphine-treated animals changed their preference on session 4, this was not repeated after the second treatment on session 7 - when fewer changes were recorded than for the controls.. Conclusions: .The results are consistent with increased switching of strategies in animals with increased mesocorticolimbic DA activity - where the learning and maintenance of strategies are seen as an aid to recall the adaptive sequence of behaviour likely to lead to the relevant baited holes