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Serotonin 5-HT2A receptor binding in platelets from healthy subjects as studied by [3H]-lysergic acid diethylamide ([3H]-LSD): intra- and interindividual variability.

In studies on platelet 5-HT2A receptor binding in patients with neuropsychiatric disorders, there has been a marked variability and a considerable overlap of values between patients and controls. The causes of the large variability in 5-HT2A receptor parameters is still unsettled. In the present study, we have quantified the intra- and interindividual variability of platelet 5-HT2A receptor binding in 112 healthy subjects and explored factors that may influence 5-HT2A receptor binding, using [3H]-lysergic acid diethylamide as radioligand. Age, gender, blood pressure, and metabolic capacity of the liver enzymes CYP2D6 and CYP2C19 did not influence Bmax and Kd values. Body weight and body mass index (BMI) showed a negative correlation with Kd (p = .04 and .03, respectively), but not with Bmax. Bmax was significantly lower in the light half of the year than in the dark half of the year (p = .001), and Kd was significantly lower in the fall than in the summer and winter (p < .001). In females, there was a significant increase in Bmax from week 1 to week 2 of the menstrual cycle (p = .03). Females taking contraceptive pills had significantly higher Kd than drug-free females in weeks 1 and 4 of the menstrual cycle (p = .04). This study shows that a number of factors should be taken into account when using platelet 5-HT2A receptor binding in studies of neuropsychiatric disorders.

Adolescent↗

Effects of lysergic acid diethylamide (LSD) and adjuvant-induced inflammation on desensitization to and metabolism of substance P in the mouse spinal cord.

We have previously shown that the caudally directed biting and scratching response to repeated intrathecal (i.t.) injections of substance P (SP) is decreased by the third injection of SP and that this apparent desensitization to SP is less pronounced in mice pretreated with Freund's adjuvant. This study was designed to study the mechanism of this desensitization to SP and to examine the effect of lysergic acid diethylamide tartrate (LSD) on desensitization. Our results indicate that while 25 micrograms of LSD/kg body weight i.p. in naive mice had no effect on the response to a single injection of SP, LSD decreased the development of desensitization to SP-induced behaviors. In contrast, identical injections of LSD in adjuvant-pretreated mice not only failed to prevent desensitization but enhanced the degree of apparent desensitization to SP. Tolerance developed to the effects of LSD on desensitization to SP-induced behaviors in both adjuvant- and saline-pretreated mice. When injected i.t. with SP, LSD failed to alter the degree of desensitization to SP-induced behaviors, suggesting that the effect of LSD is not produced at the spinal cord level. Separation and quantification of SP and its metabolites in the spinal cord using high performance liquid chromatography (HPLC) techniques indicated that either a single injection of LSD or pretreatment with Freund's adjuvant produced similar patterns of changes in the concentrations of SP-related peptides in mouse spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗