Jon M. Stolk

Parachlorophenylalanine and habituation to repetitive auditory startle stimuli in rats

Abstract The relationship between brain serotonin levels and habituation of a skeletal-motor startle response was studied using parachlorophenylalanine (PCPA), a drug which inhibits the formation of serotonin. Depletion of brain serotonin by PCPA slows down, but does not prevent, habituation. PCPA given to rats that were habituated before starting drug treatment causes a transitory increase in startle response magnitude. Whether PCPA is administered before or after habituation, the treated rats exhibit heightened reactivity to startle stimuli following exposure to novel stimuli. These results suggest that brain serotonin plays a role in inhibitory processes.

Species differences in methemoglobin reductase activity

Abstract Sodium nitrite induced equivalent levels of methemoglobin in washed erythrocytes from cat, dog, and man, all suspended in Krebs-Ringer phosphate-glucose (pH 7·4). The same levels occurred in human cells with or without aded substrate (glucose or lactate). In all these incubations, reduction of methemoglobin was minimal or absent over a 2-hr period. When 10−5M methylene blue was added with glucose, equivalent increases in rates of methemoglobin reduction occurred in the cells of all three species. Similar rates were seen in rabbit and mouse red cells even without added methylene blue, as long as lactate or glucose was present. Methylene blue further enhanced reductase activity in mouse cells but only in the presence of glucose. Rabbit cells responded much less dramatically, if at all, to methylene blue. Lysates of human, rabbit, and mouse cells were equally sensitive to nitrite, and no spontaneous reduction occurred. These findings suggest that the high reductase activity of rabbit and mouse erythrocytes is NADH-dependent. The mouse but not the rabbit appears to possess also a NADPH-dependent reductase like man, dog and cat.

The effect of parachlorophenylalanine (PCPA) on shock-induced fighting behavior in rats

Abstract Shock-induced fighting behavior was studied in rats treated with parachlorophenylalanine (PCPA). In the doses used, PCPA injections depleted brain serotonin to 10 per cent of the control animal levels. In the first study, injections were started prior to initial behavioral testing. In the second experiment, injections were started during a sequence of repeated behavioral testings in the shock-induced fighting situation. In neither case was there any evidence that PCPA injections had any effect on shock-induced fighting behavior in rats.

Rubidium-induced increase in shock-elicited aggression in rats

Daily treatment of rats with 0.3 or 0.6 meq/kg rubidium chloride (RbCl) causes an increase in shock-elicited aggressive behavior relative to potassium chloride-treated controls. Aggressive responses increase immediately with the higher dose of RbCl and are maintained for 12 days. The lower RbCl dosage increases fighting behavior significantly after 11 consecutive injection days. Measurements of flinch, jump, and vocalization threshold reveal no consistent pattern with treatment; thus, it is unlikely that threshold changes underlie the observed increases in aggression.

Species differences in amphetamine toxicity: Effects of aggregation, acute and chronic reserpine pretreatment in mice and rats☆☆☆

Abstract Marked differences in amphetamine toxicity between rats and mice are presented. The major differences can be summarized as follows: 1. 1. The effect of aggregation on amphetamine toxicity, while prominent in mice, is not a factor in rats. 2. 2. The protective effect of a single dose of reserpine has been confirmed in grouped mice. The rat, however, shows an increased susceptibility to some doses of amphetamine under these conditions. 3. 3. A dramatic increase in the lethality of amphetamine is produced in rats chronically treated with reserpine. This effect is equivocal in mice.

Inhibition of brain dopamine-β-hydroxylase activity by methimazole

Abstract Rat brain dopamine-β-hydroxylase (DβH) activity was estimated using graded doses of 3 H-dopamine injected intracistermally. Animals treated acutely with methimazole, 5 to 50 mg/kg (.044 to .44 millimole/kg), displayed a dose-related decrease in the levels of 3 H-norepinephrine formed from 3 H-dopamine. The ID 50 of methimazole was 10 mg/kg (.088 millimole/kg). The duration of DβH inhibition, which was accompanied by a decrease in endogenous norepinephrine concentration, was between 6 and 12 hours following a single acute 10 mg/kg dose of methimazole. Methimazoles effect on DβH is thought to be mediated via its ability to chelate copper.

Differentiation of adrenomedullary catecholamine synthesizing enzyme responses to repeated immobilization in hybrid rats

Abstract The response of adrenomedullary catecholamine synthesizing enzymes to repeated immobilization was studied in hybrid (F 1 ) offspring of 2 inbred rat strains (LEW and F344). Immobilization-induced increases in tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyl-transferase (PNMT) activities in one of the parental strains (F344) previously were shown to be dependent upon intact adrenal gland innervation but independent of the pituitary gland, while responses in the other parental strain (LEW) were independent of adrenal innervation but dependent upon pituitary function. Factors determining immobilization-induced increases in adrenal enzymes of F 1 offspring were enzyme-specific. Increased PNMT activity was pituitary dependent in F 1 rats, whereas increased TH and DBH activities after immobilization were dependent upon an intact adrenal gland innervation. These results suggest that the factor(s) regulating PNMT responses are differentiable from those regulating TH and DBH responses. The results also indicate that analysis of PNMT responses to immobilization in backcross populations is feasible, and could indicate whether strain-specific response mechanisms are heritable.

Axoplasmic transport of norepinephrine in the rat brain.

Abstract { 3 H} Norepinephrine is synthesized from { 3 } dopamine injected stereotaxically into the locus coeruleus of the rat, and subsequently is transported to the anterior hypothalamus at a rate of 0.9 mm/hr. Transport occurs within the median forebrain bundle and is blocked by 6-hydroxydopamine-induced lesions in the bundle.

STRAIN-SPECIFIC MECHANISMS REGULATING ADRENAL CATECHOLAMINE SYNTHESIZING ENZYMES DURING REPEATED IMMOBILIZATION STRESS

ABSTRACT The mechanisms regulating responses of tyrosine hydroxylase (TH), dopamine- beta- hydroxylase (DBH) and phenylethanolanune-N-methyltransferase (PNMT) activity in rat adrenal medulla to repeated immobilization stress are strain specific. The increases in all 3 enzymes following stress are mediated neuronally in the F344 strain, whereas in LEW rats an intact pituitary is necessary to demonstrate increased enzyme activity. Initial results in LEW x F344 hybrid offspring demonstrate that increases in TH and DBH activity after immobilization still occur after hypophysectomy, whereas the expected increase in PNMT activity does not. The data suggest that the mechanisms responsible for altered adrenomedullary enzyme activity are determined genetically, and that PNMT is under independent control.

BRAIN STEM NOREPINEPHRINE: BEHAVIOURAL AND BIOCHEMICAL DIFFERENTIATION OF RESPONSES TO FOOTSHOCK IN RATS

Publisher Summary This chapter describes the behavioral and biochemical differentiation of responses to footshock in rats. Norepinephrine (NE) turnover and metabolism in the brain stem of male Long-Evans rats subjected to electric footshock either with or without another rat are studied. Turnover of brain stem norepinephrine was estimated over the one hour period after Shock, and Fighting rats were removed from the shock chamber. In contrast to the lack of change in fighting rats observed immediately following shock presentation, norepinephrine turnover over the subsequent hour was increased substantially. Conversely, 3H-norepinephrine turnover in brain stem of Shock rats, which increased during the shock period itself, was significantly slower than both Control and fighting group norepinephrine turnover. These results clearly differentiate the two groups exposed to electric footshock, whether on a biochemical, or a behavioral basis, and suggest that brain stem norepinephrine containing neurons participate actively in the behavioral responses evoked by electric footshock.