SPATIAL MEMORY IMPAIRMENT INDUCED BY LESION OF THE MESOHIPPOCAMPAL DOPAMINERGIC SYSTEM IN THE RAT

The hippocampal formation has long been thought to play a role in lear ning and memory. Previous studies from our laboratory examined the org anization of mesencephalic projections to the hippocampal formation in the rat. In order to evaluate the effects on learning and memory of r etrograde selective lesions of mesencephalic dopaminergic neurons, fol lowing bilateral injection of 6-hydroxydopamine in the dorsal and vent ral subiculum and adjacent CAI field of the hippocampal formation, you ng adult Sprague-Dawley rats were trained in classical inhibitory avoi dance, inhibitory avoidance using a multiple trial (training to criter ion) and the standard Morris water maze task (cued and spatial version s). With regard to inhibitory avoidance, retention was examined one, t hree and 10 days after training. Concerning the Morris water maze task , 6-hydroxydopamine-lesioned and sham-operated rats received four trai ning trials on each of four days. After training sessions, the rats we re tested during a 60-s probe trial (free-swim trial) in which the pla tform was removed from the maze. The loss of mesencephalic dopaminergi c neurons in the 6-hydroxydopamine-lesioned rats, compared to sham-ope rated rats, was verified by tyrosine hydroxylase immunohistochemistry. Although the 6-hydroxydopamine-lesioned rats were indistinguishable f rom sham-operated rats in performing the inhibitory avoidance and the cued version of the Morris water maze task, in the spatial version of the Morris water maze, lesioned rats, compared to controls, exhibited significant differences in the latency (P < 0.05), quadrant time (P < 0.01) and number of platform crossings (P < 0.05). These results sugge st that the rat's ability to acquire spatial,learning and memory for p lace navigation in the Morris water maze is likely to be dependent als o on the integrity of mesohippocampal dopaminergic connections. Copyri ght (C) 1996 IBRO. Published by Elsevier Science Ltd.