Ž . Brain Research 850 1999 14–20 www.elsevier.comrlocaterbres Research report Melatonin acts on the nucleus accumbens to increase acetylcholine release and modify the motor activity pattern of rats Daniel Paredes a , Pedro Rada b , Ernesto Bonilla a , Luis E. Gonzalez b , Marco Parada b , Luis Hernandez b, ) a Instituto de InÕestigaciones Clınicas, Facultad de Medicina, La UniÕersidad del Zulia and INBIOMED-FUNDACITE, Apartado 1151, Maracaibo, ´ Venezuela b Departamento de Fisiologıa, UniÕersidad de los Andes, Apartado Postal 109, Merida 5101, Venezuela ´ ´ Accepted 17 August 1999 Abstract Ž . Brain microdialysis coupled to high performance liquid chromatography with electrochemical detection HPLC–ED was used to Ž . Ž . evaluate the influence of melatonin on extracellular concentration of acetylcholine ACh in the nucleus accumbens NAc of rats. Motor activity was simultaneously monitored during the dialysis sessions with an activity meter. Melatonin and prazosin were administered Ž . locally through the dialysis probe. It was found that melatonin dose-dependently increased accumbens ACh. Melatonin 3 mM decreased Ž . horizontal activity and increased vertical activity, while another dose 100 mM enhanced both horizontal and vertical activity. Prazosin, a putative melatonin antagonist, blocked the effects of melatonin on both motor activity and ACh release when given 20 min before melatonin. Overall, these results suggest that melatonin modulates the release of ACh in the NAc and the pattern of motor activity in the rat. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Melatonin; Acetylcholine; Nucleus accumbens; Motor activity 1. Introduction Melatonin is a hormone primarily secreted from the pineal gland and has been implicated in the modulation of several behavioural processes such as locomotor activity w x and emotionality 11,20 . In particular, it has been found that direct injections of melatonin into the nucleus accum- Ž . bens NAc decrease motor activity and this effect is wx reversed by antidepressants 8 . This effect of intraaccum- bens melatonin on motor activity has been used as a model w x of depression 6,7,9 . The NAc is localized beneath the rostral caudate–puta- w x men and above the olfactory tubercle 21 . It is considered an anatomical interface between the limbic and motor w x systems 15 . The cholinergic neurons in the NAc are ) Corresponding author. Fax: q58-74-638304 believed to constitute circuits of interneurons intrinsically w x organized 3,21 . Cholinergic neurotransmission in the striatum seems to w x modulate motor activity. Watanabe and Shimizu 19 found that anticholinergic agents increased both striatal acetyl- Ž . choline ACh release and motor activity. These results wx were later confirmed and extended by Day et al. 5 who reported that scopolamine increased ACh concentrations in dialysates from the striatum, hippocampus and cortex and the ACh levels were correlated with locomotor activity. Few studies have looked at the relationship between ac- cumbens ACh and motor activity. Intraperitoneal scopo- lamine induced an increase in extracellular ACh levels in the NAc and such a change was accompanied by an w x increase in locomotion, rearing and grooming 18 . Even though melatonin and ACh influence locomotor activity, the interaction between melatonin and cholinergic transmission in the central nervous system has been scarcely investigated. Furthermore, no data have been pub- lished on the effect of melatonin on accumbens ACh. The 0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01992-7