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Topographic EEG changes during treatment with lithium (Li), carbamazepine (CBZ), and clomipramine (CMI)
160A
BIOL PSYCHIATRY 1990;27:41A-179A
Lithium and Mania
STUDIES IN LITHIUM AND MANIA Saturday, M a y 12, 1 : 0 0 - 6 : 0 0 P M
Versailles Ballroom
268 TOPOGRAPHIC EEG CHANGES DURING TREATMENT WITH LITHIUM (Li), CARBAMAZEPINE (CBZ), AND CLOMIPRAMINE (CMI) Joyce G. Small, M.D., Victor Milstein, Ph.D., Marvin J. Miller, M.D. (by invitation), Jeffrey J. Kellams, M.D., Jon D. MarherLke, M.D. (by invitation), Iver F. Small, M.D. 1315 West lOth Street, Indianapolis, IN 46202. Topographic, waking EEG studies were obtained after a 2 week drug washout in 15 manic, 23 depressed, and 12 obsessive-compulsive (OCD) patients. All patients were restudied after 8 weeks of drug treatment consisting of Li or CBZ in the manics; Li, CBZ, or Li combined with CBZ in the depressed patients; and CMI for OCD. Standard clinical assessments were obtained and the patients with affective disorders received concomitant neuropsychological tests. EEG maps in lithium-treated manics showed discrete EEG changes in different locations depending upon frequency. In contrast, CBZ generated widespread EEG changes. CMI produced significant increases in most frequencies, but these were confined to the dominant hemisphere. Further analyses showed no essential differences among the diagnostic groups nor any significant baseline asymmetries. However, unique regional EEG changes were associated with therapeutic response.
269 IN-VIVO EVIDENCE THAT CHRONIC LITHIUM DECREASES CORTICAL BETA-ADRENOCEPTOR-STIMULATED cAMP PRODUCTION Jose Bitran, Monica Masana, John K. Hsiao, Ivan N. Mefford, William Z. Potter Section on Clinical Pharmacology, Neuroscience Branch, National Institute of Mental Health, Bethesda, bid 20892. Lithium has been shown to blunt beta-adlenoceptor-stimulated cyclic AMP (cAMP) production in cortical slices and membranes, but the physiological relevance of these findings has been questioned. A method for assessing in-vivo beta-adrenoceptor-linked cAMP production would have considerable utility. In the present study, in-vivo beta-adrenoceptor-stimulated cAMP production was assessed using microdialysis. Microdialysis probes were implanted in the frontal cortex of chloral hydrate anesthetized, male Sprague-Dawley rats, and peffused at ! ~tl/min witb artificial CSF containing 0.3 ~M of the phosphodiesterase inhibitor rolipram. Basal cAMP was detectable in dialysate and addition of 10"4 M norepinephrine (NE) increased cAMP recovery by 2- to 3-fold. This was blocked by the addition of proranolol, and there was a dosedependent relation (from 10.5 to 10-3 M NE). Addition of isoproterenol to peffusate also stimulated cAMP recovery. These results are consistent with those of other investigators and confirm that microdialysis can be used to assess in-vivo beta-adrenoceptor-linked cAMP production. To assess the effects of lithium treatment, male Sprague-Dawley rats were fed either regular or lithium-supplemented chow for 8 weeks. Lithium levels in the treated rats averaged 0.6 mEq/liter. NE-stimulated cAMP recovery in the lithium rats was 62% that of placebo-treated rats (p < 0.02), demonstrating that chronic lithium treatment decreases in-vivo beta-adrenoceptor-stimulated cAMP production.
BIOL PSYCHIATRY 1990;27:41A-179A
Lithium and Mania
STUDIES IN LITHIUM AND MANIA Saturday, M a y 12, 1 : 0 0 - 6 : 0 0 P M
Versailles Ballroom
268 TOPOGRAPHIC EEG CHANGES DURING TREATMENT WITH LITHIUM (Li), CARBAMAZEPINE (CBZ), AND CLOMIPRAMINE (CMI) Joyce G. Small, M.D., Victor Milstein, Ph.D., Marvin J. Miller, M.D. (by invitation), Jeffrey J. Kellams, M.D., Jon D. MarherLke, M.D. (by invitation), Iver F. Small, M.D. 1315 West lOth Street, Indianapolis, IN 46202. Topographic, waking EEG studies were obtained after a 2 week drug washout in 15 manic, 23 depressed, and 12 obsessive-compulsive (OCD) patients. All patients were restudied after 8 weeks of drug treatment consisting of Li or CBZ in the manics; Li, CBZ, or Li combined with CBZ in the depressed patients; and CMI for OCD. Standard clinical assessments were obtained and the patients with affective disorders received concomitant neuropsychological tests. EEG maps in lithium-treated manics showed discrete EEG changes in different locations depending upon frequency. In contrast, CBZ generated widespread EEG changes. CMI produced significant increases in most frequencies, but these were confined to the dominant hemisphere. Further analyses showed no essential differences among the diagnostic groups nor any significant baseline asymmetries. However, unique regional EEG changes were associated with therapeutic response.
269 IN-VIVO EVIDENCE THAT CHRONIC LITHIUM DECREASES CORTICAL BETA-ADRENOCEPTOR-STIMULATED cAMP PRODUCTION Jose Bitran, Monica Masana, John K. Hsiao, Ivan N. Mefford, William Z. Potter Section on Clinical Pharmacology, Neuroscience Branch, National Institute of Mental Health, Bethesda, bid 20892. Lithium has been shown to blunt beta-adlenoceptor-stimulated cyclic AMP (cAMP) production in cortical slices and membranes, but the physiological relevance of these findings has been questioned. A method for assessing in-vivo beta-adrenoceptor-linked cAMP production would have considerable utility. In the present study, in-vivo beta-adrenoceptor-stimulated cAMP production was assessed using microdialysis. Microdialysis probes were implanted in the frontal cortex of chloral hydrate anesthetized, male Sprague-Dawley rats, and peffused at ! ~tl/min witb artificial CSF containing 0.3 ~M of the phosphodiesterase inhibitor rolipram. Basal cAMP was detectable in dialysate and addition of 10"4 M norepinephrine (NE) increased cAMP recovery by 2- to 3-fold. This was blocked by the addition of proranolol, and there was a dosedependent relation (from 10.5 to 10-3 M NE). Addition of isoproterenol to peffusate also stimulated cAMP recovery. These results are consistent with those of other investigators and confirm that microdialysis can be used to assess in-vivo beta-adrenoceptor-linked cAMP production. To assess the effects of lithium treatment, male Sprague-Dawley rats were fed either regular or lithium-supplemented chow for 8 weeks. Lithium levels in the treated rats averaged 0.6 mEq/liter. NE-stimulated cAMP recovery in the lithium rats was 62% that of placebo-treated rats (p < 0.02), demonstrating that chronic lithium treatment decreases in-vivo beta-adrenoceptor-stimulated cAMP production.