Lithium inhibition of norepinephrine and dopamine receptors.

Sprague-Dawley rats (150-200 g), serving as their own controls, were evaluated for hyperactivity (HyA) and stereotyped behavior (SB) produced by chronic (1 week) ip administration of different doses of drugs that have differential NE and DA " agonist" properties. Drugs utilized were d- and l-amphetamine, metamphetamine, cocaine, and the specific and direct DA receptor agonist apomorphine. This was followed by 1 week of rest after which all rats received 3 weeks of lithium chloride (Li) subcutaneously. In the last week of Li administration, each rat also was given the same drug administered previously at the same dose. In all cases, Li decreased both HyA and SB, suggesting Li effects both at the pre- and postsynaptic neuron (receptor).

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Lithium erythrocyte/plasma ratio as a predictor of response.

The authors measured RBC/plasma lithium ratios in 33 patients with primary diagnoses of unipolar depression (N=20), bipolar depression (N=9), schizo-affective psychosis (N=2), and alcoholism (N=2). Subjects rated as having marked or moderate improvement at follow-up (average = 17.1 months) tended to have high ratios (greater than or equal to .41), whereas all 9 patients rated as minimally improved were in the low-ratio group. Although further research with larger samples, controls, and longer follow-up is necessary, the results suggest a predictive value for the RBC/lithium ratio.

Delirium associated with combined fluphenazine-clonidine therapy.

The authors report a case of acute organic brain syndrome in a patient being treated with clonidine and fluphenazine that cleared when clonidine was discontinued. Theoretical considerations of dopamine-norephinephrine interactions are discussed in the context of the drug-drug interaction.

Failure of apomorphine to induce dopamine receptor hypersensitivity.

Apomorphine, a direct dopamine agonist, failed to induce the so called dopamine receptor supersensitivity. Furthermore, a review of the evidence strongly suggests that the mechanisms involved in this phenomenon are not purely dopaminergic. This phenomenon is more complex than one of simple changes in the sensitivity or number of a particular type of receptor. Also sexual differences were observed and the literature suggest an involvement of serotoninergic mechanisms in sterotyped behavior.

Antagonism of behavioral effects of cocaine by lithium.

Ten rats, serving as their own controls, were tested for hyperactivity (HyA) (by number of turns of an activity wheel cage) and stereotyped behavior (SB). The animals were given one week each of acclimation to the cages, saline, cocaine (19 mg/kg in 1 cc/kg saline), rest, two weeks on LiCl, and a week on LiCl plus the same dose of cocaine. LiCl produced a nonsignificant decrease of HyA and significantly decreased cocaine SB. The same procedure was duplicated using two different doses of cocaine in five animals each with identical results. The author concludes that Li seems to inhibit cocaine effects in animals and suggests a potential area of research for the use of Li in humans.

Dopamine receptors hypersensitivity: further confirmation following drug abuse model.

Controversial multiple investigations have reported that chronic administration of amphetamine or similar drugs in different animals produces a reverse tolerance or a receptor hypersensitivity. However, most studies utilized large doses given chronically and for lengthy periods of time. Real life drug abusers ten to utilize drugs in a cyclic pattern of intermittently increasing doses and then "crashing off" depending on the availability of drugs and psychiatric treatment. In this experiment I intended to demonstrate receptor hypersensitivity with less chronic administration of drugs (in this case only six dosages) given in about two weeks, intermittently, and in increasing dosages to stimulate somewhat closer a drug abuse model. I also utilized a lengthier period of time of waiting in-between the pretreatment and post-treatment evaluation (eight weeks). The subjects were 16 Sprague-Dawley rats of initial weight of 150-200 grams, acclimated to photoelectric cell cages. They were given either D- or L-amphetamine in alternating days for two weeks and in increasing dosages. Both activity and stereotype behavior (SB) were measured. The animals were given eight weeks of rest and then retested with a subthreshold dose of the same drug previously utilized and two days later with the smallest dose of the same medication again. The results showed that the latency and the threshold was decreased and the response was maximized but this was statistically true only for SB, as it did not reach statistical significance for hyperactivity. The relationship of this phenomenon of dopamine receptor hypersensitivity and the clinical findings in dyskinetic disorders, is discussed; also some ideas for further research in this area are brought to light.

Field dependence, blood uric acid and cholesterol.

A preliminary report of the correlation of field dependence, blood uric acid, and cholesterol is presented here for 65 recently admitted patients to the psychiatric services of the University of Minnesota. The values for all three variables were taken once within 24 to 48 hr. after admission and prior to drug treatment whenever possible. Results are suggestive that the initial hypothesis; high blood uric acid, low-cholesterol individuals are more field-independent and high-cholesterol, low blood-uric acid individuals are more field-dependent holds, although this difference is mostly influenced by the values of cholesterol. Probably because of the small number of subjects tested no relationship could be observed with blood types used as genetic markers. Further controlled studies are suggested and are currently being carried out.

Field dependence and blood cholesterol: an expansion.

In a pilot study of 65 newly admitted psychiatric patients the first author evaluated the relationship between cholesterol, uric acid, and field dependence. The results suggested that high uric acid and low cholesterol individuals were more field independent whereas low uric acid and high cholesterol individuals were more field dependent. However, the differences were influenced mostly by the values of cholesterol and little by the uric acid. We have now expanded the sample to 229 consecutive admissions excepting only in-patients that were alcoholics or taking medication that has effects on any of the dependent variables. Included were age, ponderal index (a ratio of height and weight), and sex. For the whole group, field dependence correlated highly with age and cholesterol but less with blood uric acid. Dividing the sample by sex the situation changed. For males field dependence did not correlate with any of the other variables. However, for the females field dependence showed a positive correlation with cholesterol and age and with cholesterol even after correcting for age. Diagnoses did not correlate with any other variables except field dependence as an analysis of variance showed an incrase of field dependence when the patients were divided into three groups: (1) schizophrenics, (2) miscellaneous (including personality disorders), and (3) affective disorders. Again, these results demonstrated no relationship of field dependence with blood uric acid.