Catecholamine uptake in cerebral cortex: adaptive change induced by fighting.

The name of the senior author of "Catecholamine uptake in cerebral cortex: an adaptive change induced by fighting" (8 June 1973, page 1050) was misspelled. It should be Edith D. Hendley and not Edith D. Henley.

Catecholamine uptake in cerebral cortex: adaptive change induced by fighting.

Kinetics of the catecholainine uptake process in brain were altered by fighting. Significant increases in the apparent Michaelis constant (Km) for the uptake of norepinephrine into cerebral cortical homnogenates and significant increases in the inhibition constant (Ki) for d-amphetamnine inhibition of this uptake occurred in group-caged mice living under chronic attack from aggressive cage mates. Also, significant increases in the apparent Km and maximum velocity (Vmax) for norepinephrine uptake were observed 18 to 20 hours after the last of a series of short intense daily fights between male mice previously made aggressive by long-term individual caging. These results suggest that the natural stress of fighting leads to (i) lowered affinity for reuptake of norepinephrine into nerve endings of the cerebral cortex, (ii) an increase in the number of uptake sites, and (iii) lowered affinity for d-amphetamine.

beta-Endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa).

Small doses of the opiate antagonist naloxone selectively abolished overeating in genetically obese mice (ob/ob) and rats (fa/fa). Elevated concentrations of the naturally occurring opiate beta-endorphin were found in the pituitaries of both obese species and in the blood plasma of the obese rats. Brain levels of beta-endorphin and Leu-enkephalin were unchanged. These data suggest that excess pituitary beta-endorphin may play a role in the development of the overeating and obesity syndrome.

Genetic analysis of the behavioral response to d-amphetamine in mice.

The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57Bl/10J, and C57BL/LBy. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C5BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although th of l-dihydroxyphenylalanine (L-dopa) and d,l,5-hydroxytryptophan (d,l,5-HTP) on reserpine-induced amnesia.

Genetic analysis of the behavioral response to d-amphetamine in mice.

The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57BL/10J, and C57BL/6By. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C57BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although the genetic analysis is not conclusive, it appears to be compatible with regulation by a single major gene. The two single-gene models reported here (one affecting the stimulatory response and the other the inhibitory response to d-amphetamine) may be useful in the study of neural mechanisms involved in stimulation and inhibition of behavior by d-amphetamine.

Factors contributing to the modulation of norepinephrine uptake by synaptosomes from mouse brain cortex.

The mode of inheritance of the synaptosomal mechanism for uptake of norepinephrine (NE) was studied in two inbred strains of mice, BALB/cBY and C57BL/6BY, along with the reciprocal F1 hybrids and 7 recombinant inbred strains, CXBD, CXBE, CXBG,CXBH,CXBI,CXBJ and CXBK. All these strains were also tested in the open field as a measure of response to mild stress, since stress had been shown to affect the kinetic constants of synaptosomal uptake. The two parental strains show a significant difference in Km for NE uptake similar to that previously reported between BALB/cJ and C57BL/10J, and no significant difference in V max. The F1 hybrids resemble C57BL/6BY, and the recombinant inbred strains show no significant differences from either parent with only minor exceptions. This makes further genetic analysis impossible with the data available at this time. A high positive correlation exists between Km and Vmax (r=0.89). The affinity for NE uptake and the number of uptake sites available seem to be modulated in a coordinated fashion. When the data on Km for all strains tested are pooled, a bimodal distribution is apparent. There are two populations with means of 2.25 and 4.03 x 10-7 M, respectively. Analysis of open field ambulation enables the strains to be divided into a high (C57BL/6BY, BXCF1, CXBF1, CXBD, CXBE, and CXBK) and a low group (BALB/cBY, CXBG, CXGH, CXGI and CXBJ). There is a significant negative interstrain correlation (r=0.87) between open field ambulation and Km for NE uptake. If we take open field ambulation as an index of reactivity to stress (high ambulation-low reactivity and vice versa), then we can regroup the data on NE uptake into two categories: 78% of the mice from the highly reactive strains presents high Km for NE uptake, while only 35% of the non-reactive mice show high Km. The bimodal distribution is apparent in both cases and the means of both high Km groups are identical; the same is true of the means for both low Km groups of strains of mice. It appears that Km for NE uptake does not vary along a continuum but it presents two discrete values. This would be suggestive of the existence of two distinct conformational states for the presumably proteinic uptake site. Stress presumably causes a switch from the high affinity conformation to the low affinity conformation. Thus a higher percentage of individuals from strains highly reactive to stress shows low affinity for NE uptake.

Increase in pituitary melanocyte-stimulating hormone activity of genetically obese (ob/ob) mice.

Melanocyte-stimulating hormone (MSH) activity was measured in the pituitaries of genetically obese and lean control mice using the frog skin bioassay. Obese mice pituitaries demonstrated very significantly elevated levels of biologically active MSH when compared to their lean littermates. These results support the hypothesis that the elevated levels of pituitary hormones found in obese mice possesses true biological activity.