Biomedical subjects

G B Freeman

Publications and source records attributed to G B Freeman.

23 records · Page 2Linked to original sources

PubMed1985

Brain amines and effects of chlordiazepoxide on motor activity in response to stress.

The effect of chlordiazepoxide (CDP) on emotional responsiveness to stress was determined in CD-1 male mice. The relationship of the monoamines to the mediation of emotional behavior was examined with drugs having selective actions on serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Emotional behavior as measured by locomotor activity was increased by stress. This activation enhanced the stimulatory effect of low doses of CDP (5 and 10 mg/kg) and attenuated the depressant action of higher doses (20 and 40 mg/kg). Quipazine (0.5 mg/kg) reduced the depressant effect of CDP in stressed animals. Its action failed to support a proposed anti-serotonergic action of CDP and implicated possible dopaminergic involvement. In stressed mice, apomorphine (0.5 mg/kg) and clonidine (0.1 mg/kg) antagonized the stimulatory action of low doses of CDP. Behavioral effects of clonidine provide support for the notion that the stimulatory effects of CDP may be due to enhanced catecholamine (CA) neurotransmission. Whole brain levels of NE and DA were significantly increased when clonidine was combined with CDP. This indicated a possible reduction in CA turnover and activity.

Animals↗

PubMed1981

Amrinone metabolism.

High-performance liquid chromatographic methods for the analysis of amrinone in plasma and for both amrinone and its N-acetyl metabolite in urine were developed and applied to measure specimens obtained from a number of healthy men who had received intravenous or oral amrinone. The intravenous doses ranged from 0.8 to 2.2 mg/kg. Terminal elimination of amrinone from the bloodstream followed apparent first-order kinetics. Half-life, after the drug had distributed to the tissues, was estimated by a log-linear least-squares regression; mean half-life was 2.6 +/- 1.4 hr. During the first 24 hr after medication, unchanged amrinone excreted in the urine of these subjects represented 10% to 40% of the dose. N-Acetyl metabolite in the urine represented less than 2% of the dose. In the oral study, doses ranged from 25 to 250 mg (0.31 to 3.5 mg/kg) and the maximum plasma concentration attained was proportional to the dose. The first order terminal elimination half-life was possibly dose-related. In only one subject were there unequivocal amounts of the N-acetyl metabolite in the plasma.

Aminopyridines↗

PubMed1978

Activity analysis of operant behavior following methylphenidate administration.

13 male Long-Evans hooded rats were tested on a CRF-50 reinforcement schedule. Total response time as well as time and total activity responses away from the bar were significantly influenced by injections of methylphenidate (1.2 mg/kg I.P.). In general, the data supported previous findings of reduced response rate to the drug. However, methylphenidate (a CNS stimulant) increased activity that was not related to bar pressing. Analysis of activity response to drug should include total time and activity as well as operant rates.

Animals↗

PubMedDate not supplied

Selective alteration of mouse brain neurotransmitter release with age.

The release of acetylcholine (ACh), glutamate (GLU) and dopamine (DA) from various brain regions was investigated in young (3 month) and old (30 month) Balb/c mice. Aging increased the basal release of GLU (77%) and DA (29%) in striatum and GLU in hippocampus (94%); the concentrations of these neurotransmitters in the media after K+ stimulation were unaltered by aging. Although the basal release of ACh was not altered by age, K+-stimulated ACh release was reduced in striatum. The age-related increases in basal GLU and DA release may be important in the pathophysiology of cell death during aging.

Acetylcholine↗

PubMedDate not supplied

Effect of age on behavioral and enzymatic changes during thiamin deficiency.

Open field behavior and whole brain enzymatic activities were determined during thiamin deficiency in two strains of young, as well as in aged mice. In young CD-1 mice, thiamin deficiency reduced total distance traveled and vertical movements after 7 days and the decline was more than 50% by day 9. The behavioral deficit was highly correlated to decreases in 2-oxoglutarate dehydrogenase activity (KGDH). The open field behavior of Balb/c mice was about 40% less than in CD-1 mice and responded in a qualitatively different manner to thiamin deficiency. The activity of the Balb/c mice increased and then decreased with thiamin deficiency. The activity of 3 month old mice peaked on day 6 (126% of initial score), whereas 10 and 30 month mice showed a much greater increase (about 175% of initial scores), but on day 7. Although the activity of the thiamin dependent enzyme transketolase (TK) was affected similarly at all ages, the activity of KGDH in the aged brain was more sensitive to thiamin deficiency than in the young; KGDH activity declined 41%, 57% or 74% at 3, 10, or 30 months, respectively. Thus, the current mouse model is an attractive one to study the interaction of thiamin deficiency with aging.

Aging↗