Bruce L. Welch

Norepinephrine uptake by cerebral synaptosomes of mouse: Strain differences

Uptake of norepinephrine (NE) by the presynaptic membrane of noradrenergic neurons is a major mechanism of inactivation of this neurotransmitter 6, Drugs that inhibit this reuptake cause a prolongation of the action of NE at the receptor, and presumably this is the mechanism by which they cause an elevation of mood. This implies that the rate of uptake of NE plays an important role in the modulation of emotional behavior. I f genetic differences in the uptake mechanism of NE were found, they would contribute to an understanding of the genetic differences in emotional behavior found in man and animals. The genetic determination of emotional behavior has been studied in a number of inbred strains of mice by the open field method v,9,1°. In accordance with Broadhurst 1, a more emotional animal is one that reacts by urinating and defecating and by an inhibition of its locomotor activity when subjected to the moderately stressful novel situation of the oFen field, while a non-emotional animal is one that shows higher exploratory activity and low urination and defecation under these conditions. BALB/cJ and C57BL/10J inbred strains of mice differ widely in their open field behavior, with BALB/cJ being highly emotional and C57BL/10J nonemotional ~,4. In addition to this, BALB/cJ and C57BL/10J mice also differ in their behavioral response to D-amphetaminO 2 as measured in the open field. C57BL/10J mice showed an increase in locomotor activity in the first 4 days of testing, while BALB/cJ did not. Since amphetamine is considered to affect behavior by its actions upon release and uptake of NE, it would be possible that this strain difference in response to D-amphetamine is due to a genetic difference in NE reuptake by cerebral synaptic membranes. This paper reports strain differences in affinity for uptake of NE by crude synaptosomal preparations of 3 brain regions of male BALB/cJ and C57BL/I 0J mice,

Norepinephrine Uptake into Cerebral Cortical Synaptosomes after One Fight or Electroconvulsive Shock

Membrane affinity for the neurotransmitter norepinephrine is rapidly but reversibly decreased in nerve terminals of the cerebral cortex by intense nervous stimulation. This should adaptively facilitate alerting during acute emergency and stress. The Michaelis constant (Km) for the high-affinity active uptake of norepinephrine into crude synaptosome-rich homogenates of the cerebral cortices of mice was increased 68 percent after 15 minutes of intense fighting and 110 percent 5 minutes after a single electroconvulsive shock. These changes were no longer evident 18 to 20 hours later.

Adaptation of the Adrenal Medulla: Sustained Increase in Choline Acetyltransferase by Psychosocial Stimulation

Sustained increases were produced in adrenal choline acetyltransferase of individually caged mice by placing them into groups for 10 or 15 minutes daily for 7 to 10 days. They were left undisturbed in their individual cages for the remainder of each day. As in previous experiments of similar design, adrenal catecholamines and adrenal weight were also increased, although body weight was not affected.

ENVIRONMENTAL NOISE, "ADAPTATION" AND PATHOLOGICAL CHANGE

The body is physiologically responsive to stimulation of the auditory nerve by sound even during sleep, under anaesthesia and, indeed, even after the cerebral hemispheres have been removed (1).

Adrenal Choline Acetyltransferase Activity: Sustained Effects of Chronic Intermittent Psychological and Psychosocial Stimulation

A brief period of fighting daily can cause the preganglionic splanchnic innervation of the adrenal medulla to undergo sustained, probably reversible, changes in the ability to synthesize acetylcholine. When mice that had been made aggressive by long-term individual caging were placed together and allowed to fight for 10 to 15 min daily for 10 consecutive days, choline acetyltransferase in the adrenal gland was increased. It increased to 8.4% and 37.1 % above undisturbed controls by 1 day and 3 days, respectively, after termination of fighting, and to a maximum of 45.4% above controls after 5 days; it had decreased to 20.3% above controls by 7 days after last fighting. A decrease in enzyme activity appears to precede this adaptive increase. Choline acetyltransferase activity was lowered 17.9% 18 to 20 hours after the last of 4 consecutive days of fighting. Merely transferring mice to an empty strange cage for 10 to 15 min and then returning them to their home cage, once daily for 5 days, decreased adrenal ...