Chronic lithium attenuates dopamine D1-receptor mediated increases in acetylcholine release in rat frontal cortex.

Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Psychopharmacology (Impact Factor: 3.99). 06/1996; 125(2):162-7. DOI: 10.1007/BF02249415
Source: PubMed

ABSTRACT The effects of chronic lithium treatment on methylphenidate-, D1 dopamine receptor agonist (A-77636)-, and tactile stimulation-induced increases in frontal cortical acetylcholine release were studied in the rat using in vivo brain microdialysis. Cortical acetylcholine release in control rats was maximally stimulated by methylphenidate (1.25 and 2.5 mg/kg) to 173% and 212% above baseline, respectively. The effect of methylphenidate (2.5 mg/kg) was blocked by pretreatment with the dopamine D1 receptor antagonist SCH 23390 (0.3 mg/kg). Chronic treatment with lithium chloride (3-4 weeks) produced plasma lithium concentrations of 0.45 +/- 0.02 meq/l. Chronic lithium significantly reduced increases in cortical acetylcholine release produced by methylphenidate. Stimulation of dopamine D1 receptors with the full D1 receptor agonist A-77636 (0.73 mg/kg) increased cortical acetylcholine release. Chronic lithium significantly reduced this effect of A-77636. In contrast, lithium failed to influence the increases of cortical acetylcholine release produced by tactile stimulation. These results suggest that while lithium does not influence normal, arousal-related increase in cortical acetylcholine release, this ion selectively attenuates dopamine mediated increases and/or abnormally large increases, which in the present circumstances were pharmacologically induced. The relevance of these findings to the antimanic actions of lithium is discussed.

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    Synapse 12/2000; 38(3):355 - 362. DOI:10.1002/1098-2396(20001201)38:3<355::AID-SYN15>3.0.CO;2-E · 2.43 Impact Factor
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    ABSTRACT: Background: The effects of chronic lithium exposure on spatial memory in rats remain controversial. In this study a time course of the effects of lithium, administered systemically, on spatial memory acquisition in Morris water maze was investigated. Material and Methods: Lithium (600 mg/L) was administered to four groups of rats in their drinking water; the first group of animals received lithium for one week, the second group for two weeks, the third group for three weeks, and the fourth group for four weeks. As controls, four groups of animals received only normal drinking water for the same period of time. Toward the end of their lithium or water treatment, all animals were trained for four days; each day included one block and each block contained four trials. Test trials were conducted 48 hrs after completion of the lithium treatment. Escape latency, traveled distance and swimming speed were evaluated during testing trials. Brain tissues from animals were processed according to the standard protocols for immunohistochemical analysis. Results: Lithium treatment decreased escape latency and traveled distance, but not swimming speed, compared with controls, suggesting significant spatial memory acquisition enhancement by lithium. Quantitative analysis showed that lithium, particularly after four weeks of exposure, significantly increased the number and density of immunostained ChAT-containing (choline acetyltransferase) neurons in the medial septal area in comparison with control groups. There was also a significant correlation between the number of immunostained ChAT neurons and behavioral measures. Conclusion: These results suggest that chronic oral administration of lithium causes spatial memory acquisition improvement in rats and an increase in ChAT immunostaining levels in medial septal nuclei.