Catecholamines and conditioned blocking: effects of ventral tegmental, septal and frontal 6-hydroxydopamine lesions in rats

Abstract

Introduction: The performance of rats on the conditioned blocking test (CB) of learned inattention was measured in a two-way shuttle avoidance task after sham and dopamine (DA) - depleting lesions of the frontal cortex, the limbic septum, and the ventral tegmental area (VTA - A10). Methods: Animals were trained on two sessions with tone and / or light as conditioned stimuli. One group was trained with both stimuli on both sessions. A second group was trained on the first session with one stimulus and on the second with both stimuli. The blocking of conditioning to the added stimulus (b) was tested by presenting the stimuli (a and b) separately and measuring the blocking ration (avoidance to b/a + b) and response latencies. Results: 1/ No deficits were recorded on tests of sensory and motor ability; 2/ The VTA group alone showed a hyperlocomotor response to apomorphine treatment, - and did not acquire the avoidance response (i.e. did not learn the active avoidance task); 3/ The appearance of blocking in the septally lesioned group was delayed until the end of the 20-trial test session - then it was exaggerated; 4/ Blocking was mildly attenuated in the frontally lesioned group. 5/ Dopamine (DA) levels were depleted by about 80% and noradrenaline (NA) levels by, respectively, 20% and 50% in the frontal and septal regions. Figure 2 illustrates a) the CB impairment in the frontal group relative to sham controls, and b) the late development of "supr-blocking" in septally-damage animals. Figure 3 illustrates the results of the HPLC analysis for NA, DA and DOPAC in frontal cortex, septum, N. accumbens and striatum after 6-OHDA lesions (& vehicle treatment) in the frontal, septal, and VTA areas. Conclusions: The results show that the levels of DA activity, or rather the balance between the activity of DA and NA in frontal and limbic regions can contribute to efficient associative conditioning and / or the normal ability of rats not to attend to a redundant stimulus.