Arthur J. Prange

Neurotensin: central nervous system effects of a hypothalamic peptide.

The central administration of neurotensin, an endogenous hypothalamic tridecapeptide, produces a marked dose-related decrease in body temperature of mice and rats at an ambient temperature of 25 degrees C. This effect is even more pronounced when mice are placed at 4 degrees C to increase the rate of decline of body temperature. Other sequelae observed after central administration of neurotensin are decreases in locomotor activity in rats and a marked dose-related enhancement in pentobarbital-induced mortality, sedation and hypothermia. This latter effect was shown to be due to a significant reduction in the metabolic degradation of the barbiturate. None of the above-mentioned effects are observed after peripheral neurotensin administration, suggesting that this peptide does not readily cross the blood-brain barrier. Neurotensin appears to be one of a growing list of neuropeptides that can affect CNS function.

Thyrotropin releasing hormone: Antagonism of pentobarbital in rodents

Abstract Thyrotropin releasing hormone (TRH) antagonizes the behavioral and temperature reducing effects of pentobarbital in rodents. The hormone is effective whether given before or after the barbiturate. This antagonism by TRH of the effects of pentobarbital probably does not depend upon thyroid hormone release as L-triiodothyronine administration is ineffective.

Antagonism of ethanol narcosis by thyrotropin releasing hormone

Abstract Thyrotropin releasing hormone (TRH) reduced the narcosis and hypothermia produced by ethanol in mice. This action of TRH does not appear related to release of thyroid hormone or to the effects of a metabolite of TRH. The ability of TRH to reduce the actions of ethanol after intracisternal injection suggests that the mechanism of the ethanol antagonism is central in origin. The antagonism of ethanol by TRH does not appear to be related to an amphetamine-like stimulant action.

The effect of neurotensin on food consumption in the rat

The effect of neurotensin on feeding behavior were studied in rats. Intracerebroventricular administration of neurotensin (3.3-30 micrograms) produced a dose-related decrease in food intake in 24 h food deprived rats. Acute intracerebroventricular injection of neurotensin (30 micrograms) shortly after the ingestion of a novel flavor did not produce a flavor aversion during testing 48 h later, suggesting that reduction of food intake by low doses of centrally administered neurotensin is not related to a conditioned taste aversion. Intracerebroventricularly administered thyrotropin-releasing hormone (2.2 micrograms) also inhibited food intake and appeared to attenuate slightly the inhibition of food intake induced by 10 micrograms neurotensin.

Oxytocin potently enhances novelty-induced grooming behavior in the rat

Intracerebroventricular (i.c.v.) injection of oxytocin was followed by an enhancement of novelty-induced grooming in male and female rats. This effect was dose-dependent, in a dose range of 0.1-10 micrograms. Grooming activity of rats injected i.c.v. with 10 micrograms of oxytocin was 9-fold higher than that of saline-injected controls. The analysis of behavioral element composition revealed an increased occurrence of genital grooming in oxytocin-injected rats. A time-course study revealed a sustained increase in grooming activity of oxytocin-treated rats during 45 min of behavioral testing. Intraperitoneal (i.p.) injection of the dopamine antagonist, haloperidol, totally suppressed oxytocin-enhanced grooming. Furthermore, i.p. injection of the opiate receptor antagonist, naloxone, was followed by an attenuation but not a suppression of grooming enhanced by i.c.v. administration of oxytocin. In addition, a small but significant increase in grooming activity was observed after subcutaneous injection of oxytocin. These results suggest that oxytocin-enhanced grooming behavior involves central mechanisms, e.g. dopamine and opioid transmission in the brain.

Increase in spontaneous motor activity following infusion of neurotensin into the ventral tegmental area

Microinjection of neurotensin (NT) into the ventral tegmental area (VTA) of the rat produced a dose-dependent increase in spontaneous motor activity. The NT-induced hyperactivity consisted of an increase in exploratory behaviors, such as locomotion, rearing and sniffing, and a decrease in sleep or resting. The structural specificity of this response was demonstrated by microinjecting NT analogues endogeneous neuropeptides into the VTA. The fact that high levels of immunoreactive NT have been demonstrated in the VTA indicates that the observed behavioral effects may reflect an underlying physiological action by endogenous NT.

Influence of cholecystokinin on central monoaminergic pathways

Dopamine (DA) and cholecystokinin octapeptide carboxy-terminal (CCK-8) have been found to coexist in some mesolimbic neurons. The present investigation was undertaken in order to study the biochemical and behavioral interactions between CCK-8 and some central monoaminergic pathways. The action of the sulfated form of CCK-8 (10 micrograms/10 microliter intracerebroventricularly) on DA turnover in nucleus accumbens, olfactory tubercles and corpus striatum of the rat was determined after DA synthesis inhibition with alpha-methyl-p-tyrosine (250 mg/kg i.p.). Also, CCK-8 action (1-30 micrograms intracisternally) on DA synthesis was assessed by measuring accumulation of dihydroxyphenylalanine (DOPA) after DOPA-decarboxylase inhibition with NSD-1015 (m-hydroxybenzylhydrazine, 100 mg/kg i.p.). The contents of DA and its main metabolites, dihydroxyphenylacetic acid and homovanillic acid, together with serotonin and its main metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured in different brain areas after direct injection of CCK-8 into the ventral tegmental area (A10) or nucleus accumbens. Further, the effect of CCK-8 on amphetamine-induced locomotion and apomorphine-induced stereotypies was studied along with changes in spontaneous locomotion and rearing after CCK-8 injection into the ventral tegmental area and nucleus accumbens. No consistent statistically significant effects of CCK-8 on biochemical or behavioral assessments on measures of DA function were observed. However, injection of high doses of CCK-8 into the ventral tegmental area significantly decreased levels of 5-HIAA in the nucleus accumbens, olfactory tubercles and striatum.

Antinociception after microinjection of neurotensin into the central amygdaloid nucleus of the rat

Neurotensin (NT) is an endogenous peptide which has been hypothesized to function in the central nervous systems as a neurotransmitter. Injection of NT into the cerebral ventricular system of rodents produces antinociception in a variety of analgesia tests. In the hot plate test, direct microinjection of NT into the central nucleus of the amygdala (AC) produced a significant increase in the nociceptive threshold of the rat, while injections into tissue adjacent to the AC were generally ineffective. Antinociception following intra-AC injection of NT occurred at an ED50 dose of 2.4 micrograms NT, and was significantly lower than the ED50 dose observed when NT was given into the lateral ventricles (93.2 micrograms NT). Lesions of the stria terminalis totally abolished the antinociceptive effect of intra-AC administration of NT, indicating that AC efferent or afferent fibers within the stria terminalis are necessary for the observed increase in nociceptive threshold.

Neurotensin, a biologically active peptide

Abstract Neurotensin, a tridecapeptide appears to be localized in various parts of the brain and gut. A high affinity binding component of neurotensin to brain membranes, synaptosomes and mast cells has been reported. After peripheral administration the peptide exerts a medley of effects which appear directed mainly to glucose metabolism. In addition, complex vascular effects have also been noted including hypotensin, cyanosis, vasodilation and increased permeability. The peptide may also be associated with inflammatory events. Complex effects upon the secretion of anterior pituitary tropic hormones have been observed. After central administration neurotensin exerts several effects all of which appear to be sufficiently explained by the potent hypothermic action. The resolution of the question of which, if any, of the actions of neurotensin are involved in physiological regulation has not been achieved.

Neuroanatomical site specific modulation of spontaneous motor activity by neurotensin

Immunohistofluorescent neurotensin (NT) is found in the ventral tegmental area (VTA), and bilateral injection of NT into the VTA produces an increase in exploratory behaviors. The VTA also contains dopaminergic cell bodies with axonal projections to the nucleus accumbens. In this study it was shown that bilateral microinjection of NT (4.0 micrograms/side) into the nucleus accumbens blocked the behavioral hyperactivity produced by intra-VTA injection of NT (2.5 micrograms/side).