Psychopharmacology communications最新文献

The UV-spectrum of chlorpromazine undergoes a red shift in the presence of vesicles of biological membranes or phospholipids, triglycerides, serum lipoproteins or fatty acids. The resulting difference spectrum has two positive peaks at about 260 and 320 nm and two negative peaks at 250 and 290 nm. This interaction signal, which was elicited in the presence of as little as 3 muM oleic acid, was dependent on the concentrations of both ligand and binder. It was abolished by 8 M urea, diminished by temperature increase up to 70 degrees C, but not changed by varying the ionic strength from 0 to 0.5. The chlorpromazine-triglyceride interaction signal was strongly enhanced with pH increasing from 6 to 10. The signal was only obtained with ligands fulfilling specific structural requirements, e.g., phenothiazines and most iminostilbenes, but not carbamazepine, imipramine, and amitriptyline.

Some reports have suggested that methylation and demethylation of compounds related to 6-hydroxydopamine may be involved in endogenous mental disorder. We report the synthesis of 3,4-dimethoxyphenethylamine (DMPEA) and 2,4,5-trimethoxyphenylisopropylamine (TMA-2) with each methoxyl group separately labeled with 14C. The rate and percent demethylation of these two compounds, with five labeled positions, were determined in the rat. The results suggest that TMA-2 might be metabolized to a hydroquinone in vivo; a similar metabolic intermediate of the psychoactive compound DOM is known to give rise in vitro to an indole.

The action of d-amphetamine was studied in rats conditioned on an operant "multiple" schedule of reinforcement. The action of this drug depended on the control response rate of each individual. The turnover of brain norepinephrine (NE) and dopamine (DA) was estimated in the whole brain of the same rats; the steady state level of NE, but not the turnover time, was significantly correlated with the average response rate of each subject. No significant correlation was found between this response rate and the turnover of DA. It is proposed that the response rate dependent effects of d-amphetamine might be related to brain NE levels.

The kinetic constants, apparent Km and Vmax, for the uptake of 3H-1-norepinephrine in cerebral cortical homogenates of the rat brain were not altered 5 min after a single electroconvulsive shock (ECS). However, one day after the last of a series of 14 ECS the apparent Km and Vmax were significantly increased above sham-shock controls, and ECS rats lost weight. Three days after the last ECS apparent Km and Vmax were significantly decreased, while the rate of weight gain tripled in the ECS rats. One week after the last ECS the kinetic constants and rate of weight gain were no different from sham-shock controls. These data are indicative of the strong compensatory mechanisms in the normal rat to the alterations induced by ECS.

A highly sensitive and reproducible GLC technique for the quantitation of amitriptyline and nortriptyline is described. The lower limit of detection is less than 1 ng/ml. 5 ng/ml samples (3 ml aliquots) can be accurately quantified (C of V less than 5%). Steady state data are reported together with data on amitriptyline and nortriptyline levels obtained in a volunteer who ingested a single oral dose (25 mg) of amitriptyline (Elavil).

Self-stimulation of substantia nigra and locus coeruleus were assessed before and after an 8-day regimen in which pimozide was given twice daily at a dose of 0.5 mg/kg (first 4 days) or 1.0 mg/kg (last 4 days). At 48 hours after termination of pimozide treatment self-stimulation was increased to 25% above pre-pimozide baseline levels: this was true for both self-stimulation sites. Rates remained high the following day but returned to normal by the third day of post-pimozide-testing. These data are interpreted as reflecting pimozide-induced supersensitivity in a dopamenergic substrate. This substrate appears to be critical for intracranial self-stimulation even when its fibers are not themselves activated at the tip of the stimulating electrode.

Rats permanetly depleted of central dopamine (DA) via 6-OHDA neonatally were studied in relation to their ability to discriminate various psychoactive drugs from saline using a two-bar operant procedure. DA rats learned to discriminate both morphine (4 mg/kh) and d-amphetamine (0.9 mg/kg) as rapidly as controls and exhibited similar sensitivity when dose-generalization studies were conducted. However, DA rats appeared to tolerate higher doses of the same drug better than controls indicating that they were more tolerant to behavioral disruption. It was suggested that the behavioral disruption. It was suggested that the behavioral disruption usurons. DA rats had more difficulty learning to discriminate nicotine than controls. In fact the peripherally injected nicotine stimulus generalized to hippocampal (Hp) injections in controls but was not observed in DA rats. These data suggest that part of nicotine's discriminative stimulus properties may be contingent upon the integrity of a Hp-DA connection.

Male mice of 3 different strains (NIH, C57BR/cdJ and A/HeJ) were exposed individuality (victims) to attack by trained fighter Swiss Webster mice for 10 minutes daily for various numbers of days. Immediately after the last attack the victim mice were decapitated along with unattacked control mice of the appropriate strain, and plasma norepinephrine (NE) and epinephrine (E) were measured. The concentration of NE was significantly lower in decapitated C57BR/cdJ mice than in the other 2 strains. The concentrations of E and NE in the plasma of decapitated C57BR/cdJ and A/HeJ mice were significantly greater after 4 days of attacks, whereas in NIH mice plasma levels of only NE were greater and this occurred only after 14 days of attacks. After 7 days of exposure to attack, C57BR/cdJ and A/HeJ victim mice were permitted to rest for various periods of time. In C57BR/cdJ animals plasma E returned to almost normal levels after 2 days, and NE after 4 days, while in A/HeJ mice plasma E and NE returned to control levels already after 1 day of rest.