The effects of intrahypothalamic injections of guanethidine on catecholamine fluorescence, food intake and temperature regulation in the rat

doi:10.1016/0091-3057(73)90122-6

Pharmacology Biochemistry and Behavior

Volume 1, Issue 3, May–June 1973, Pages 307-312

https://doi.org/10.1016/0091-3057(73)90122-6 Get rights and content

Abstract

The effects of chronic injections of two dose levels of guanethidine sulphate into the lateral hypothalamus of the rat on eating, drinking, body temperature and on the levels of catecholamines as shown by fluorescence histochemistry were examined over a period of 12 days. During the guanethidine treatment, food and water intake were reduced, body temperature showed a significant rise, and the animals showed a wide loss of catecholamine fluorescence in the hypothalamic area. After cessation of injections, food and water intake as well as body temperature returned to preinjection base levels. Catecholamine fluorescence also returned during the 12 days after cessation of injections. These results are discussed in terms of current hypotheses concerning the hypothalamic adrenergic involvement in consummatory behavior and temperature regulation.

References (32)

D.D. Avery
Intrahypothalamic adrenergic and cholinergic injection effects on temperature and ingestive behaviour in the rat
Neuropharmacology
(1971)
B. Evans et al.
Long-lasting damage to the internal male genital organs and their adrenergic innervation in rats following chronic treatment with the antihypertensive drug guanethidine
Fert. Steril.
(1972)
A.F. Green
Antihypertensive Drugs
A.K.S. Ho et al.
Evidence of adrenergic-cholinergic interaction in the central nervous system II. Dopamine and its analogues
Eur. J. Pharmac.
(1972)
Z.L. Kruk
The effect of drugs acting on dopamine receptors on the body temperature of the rat
Life Sci.
(1972)
R.P. Maickel et al.
Effects of guanethidine on rat brain serotonin and norepinephrine
Pharmacologist
(1969)
G. Singer et al.
Cholinergic and adrenergic interaction in the hypothalamic control of drinking and eating behavior
Physiol. Behav.
(1972)
S. Siegal
Nonparametric Statistics: for the Behavioural Sciences
(1956)
G.P. Smith et al.
Effect of lateral hypothalamic injections of 6-hydroxydopamine on food and water intake in rats
Nature
(1972)
B.D. Berger et al.
Norepinephrine: Reversal of anorexia in rats with lateral hypothalamic damage
Science
(1971)
A.L.A. Boura et al.
Adrenergic neuron blocking agents
Ann. Rev. Pharmac.
(1965)

G. Burnstock et al.

A new method of destroying adrenergic nerves in adult animals using guanethidine

Br. J. Pharmac.

(1971)

D.A. Booth

Localization of the adrenergic feeding system in the rat diencephalon

Science

(1967)

D.A. Booth

Mechanisms of action of norepinephrine in eliciting an eating response on injection into the rat hypothalamus

J. Pharmac. exp. Ther.

(1968)

B. Chisholm et al.

A new type of cannula for central administration of drugs in rats

Physiol. Behav.

(1970)

E. Deux et al.

Emotionally induced increases in effective osmotic pressure and subsequent thirst

Science

(1970)

B. Evans et al.

Long-lasting supersensitivity of the rat vas deferens to norepinephrine after chronic guanethidine treatment

J. Pharmac. exp. Ther.

(1973)

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The role of the ventral noradrenergic bundle in relation to endorphins in the control of core temperature, open-field and ingestive behaviour in the rat
1983, Brain Research
Discrete, bilateral, radiofrequency destruction of the ventral noradrenergic bundle (VB) resulted in a pronounced fall in levels of noradrenaline in the hypothalamus but not in the cortex.
On days 4 and 12, but not 28, post-surgery, VB-lesioned rats were hyperactive (rearing and ambulation) upon exposure to a novel open-field space. This hyperactivity was greatly attenuated by naloxone, which did not significantly modify sham activity. These data suggest that the VB may be involved in the control of locomotor-exploratory activity via an interaction with an endorphinergic system.
On day 4, but not 12 or 25, VB-lesioed rats displayed a significant elevation in core temperature (Tc). No difference in the hyperthermia elicited by introduction into the open-field was, however, seen between VB-lesioned and sham rats on day 4. In both groups, this rise in Tc was strongly attenuated by naloxone. These data indicate that the VB may be involved in the control of Tc but that it does not mediate novelty-stress evoked hyperthermia, for which endorphins are primarily responsible.
Within 7 days post-surgery, VB-lesioned rats developed an enhancement of daily food intake which led to a slight obesity. From day 15 onward, a hyperdipsia was also seen in VB-lesioned rats. Naltrexone reduced the food and water intake of both sham and VB-lesioned animals but failed to totally block this hyperphagia. It is suggested that the VB is involved in the regulation of daily ingestive behaviour and that endorphins do not exclusively mediate the VB-lesion induced hyperphagia.
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1979, Pharmacology and Therapeutics
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1977, Brain Research Bulletin
The lateral hypothalamic (LH) syndrome characterized by impairment of the ability to regulate food and water intake has been reported to occur after injections of 6-hydroxydopamine (6-OHDA) into this region. In the present experiment the fluorescence histochemical technique was used to assess monoamine depletion of noradrenaline and dopamine containing neurons following intrahypothalamic injection of 6-OHDA. Results show that the intensity and area of monoamine accumulation in axons served by 6-OHDA is correlated with the severity of behavioral deficits but that actual catecholamine depletion of either the corpus striatum or the hypothalamus is unrelated to the syndrome. Possible mechanisms of action of this accumulation in producing behavioral deficits are discussed.
Effects of intracranial injections of 6-OHDA on food and water intakes, body temperature and body weight regulation in the rat
1976, Pharmacology, Biochemistry and Behavior
6-Hydroxydopamine was injected either intraventricularly (320 μm in 10 μl) or intrahypothalamically (64 μg in 2 μl) into rats kept under either free feeding or body weight reduced conditions. Intraventricular injections caused a temporary aphagia and hypodipsia in free feeding rats but daily measurements failed to reveal any long term effects; body weight reduced rats did not display the temporary aphagia but were initially hyperphagic. Injections into the more rostral hypothalamic areas of free feeding rats also showed only minimal short term effects; however, some of the body weight reduced group died within several days of injection. Injections made at more posterior loci again showed very little effect in both body weight reduced and free feeding groups; some temporary disruption of feeding occured from lesions in the proximity of the zona incerta of some free feeding animals.
Intracranial injections of 6-OHDA. Comparison of catecholamine-depleting effects of different volumes and concentrations
1976, Pharmacology, Biochemistry and Behavior
Fluorescence histochemistry was used to assess monoamine depletion after injections of 6-OHDA into selected brain areas. Two volumes (2 and 4 μl) and 4 concentrations (1, 2, 4 and 8 μg/μl) of 6-OHDA were injected into the olfactory tubercle, the posterior lateral hypothalamus and the lateral hypothalamus. Selective destruction of catecholamine-containing neurons resulted from all injections of 6-OHDA with the exception of the 2 lowest doses (2 and 4 μl of 1 μg/μl) and the highest dose (4 μl of 8 μg/μl) which produced nonspecific damage of brain parenchyma. The results indicate that, in addition to the selection of an effective dose, it is also possible to choose a site of injection which will produce a maximal area of specific depletion. In cases where injections into terminal areas caused limited specific depletion the same dose injected into preterminal axons often caused a more widespread loss of flourescence. With volume, concentration and anatomical location being important variables to consider, caution is needed in the interpretation of behavioural experiments. When using 6-OHDA it is necessary to show that specific depletion of catecholamines has been achieved.
Effects of chronic intracranial injection of low and high concentrations of guanethidine in the rat
1975, Pharmacology, Biochemistry and Behavior
Low (64 μg in 2 μl) or high (320–1280 μg in 2 μl) doses of guanethidine sulphate were injected daily for up to 19 days into the lateral hypothalamus, substantia nigra, locus coeruleus, dorsal raphe nucleus, or amygdala region of the rat brain. Effects on monoamine-containing neurons were determined using fluorescence histochemistry. The noradrenergic terminals of the hypothalamus were depleted over a diameter of 7 mm by both low and high doses of guanethidine whereas, even with high doses, the dopaminergic terminals of the median eminence, amygdala and caudate nucleus were only partially depleted. Fluorescence levels of dopaminergic cell bodies of the substantia nigra and 5HT-containing cell bodies of the dorsal raphe nucleus were unaltered by low doses of guanethidine. Low doses of guanethidine did not affect the fluorescence of the noradrenergic cell bodies of the locus coeruleus, however high doses caused a substantial reduction in fluorescence levels. Normal levels of fluorescence were observed in all catecholamine-containing neurons within 14 days from cessation of injections. Thus, the axon retraction and eventual degeneration of peripheral sympathetic adrenergic neurons, which occurs as a result of chronic intraperitoneal injections of guanethidine, does not occur with the catecholamine-containing neurons in the central nervous system. The rapid recovery of central catecholamine-containing neurons is remarkable in view of the extensive areas of brain damage produced by chronic injection of such high concentrations of drug. Fluorescence in peripheral adrenergic nerves was unaffected by chronic injection of guanethidine into the lateral hypothalamus but adhesions of some internal organs were observed. Blood vessels in the vicinity of the cannula were heavily reinnervated by fluorescent fibres probably arising from intracranial catecholamine-containing neurons. Some of the advantages of intracranial injection of guanethidine compared to 6-hydroxydopamine for behavioral experiments are discussed.

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^☆: This work was supported by Grants D65/15607 and D65/15193 from the Australian Research Grants Committee,Grant 72/1365 from the National Health Medical Research Council and Grant G906/771 from the National Heart Foundation of Australia.

²: We thank Linden Cooper and Louise Western for excellent technical assistance.

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The effects of intrahypothalamic injections of guanethidine on catecholamine fluorescence, food intake and temperature regulation in the rat☆

Abstract

Neuropharmacology

Fert. Steril.

Eur. J. Pharmac.

Life Sci.

Pharmacologist

Physiol. Behav.

Nature

Norepinephrine: Reversal of anorexia in rats with lateral hypothalamic damage

Science

Adrenergic neuron blocking agents

Ann. Rev. Pharmac.

A new method of destroying adrenergic nerves in adult animals using guanethidine

Br. J. Pharmac.

Localization of the adrenergic feeding system in the rat diencephalon

Science

Mechanisms of action of norepinephrine in eliciting an eating response on injection into the rat hypothalamus

J. Pharmac. exp. Ther.

A new type of cannula for central administration of drugs in rats

Physiol. Behav.

Emotionally induced increases in effective osmotic pressure and subsequent thirst

Science

Long-lasting supersensitivity of the rat vas deferens to norepinephrine after chronic guanethidine treatment

J. Pharmac. exp. Ther.