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Biomedical subjects

B G Hoebel

Publications and source records attributed to B G Hoebel.

At least 109 records · Page 6Linked to original sources
PubMed1984

Neurotensin: a new 'reward peptide'.

oeurotensin (NT) is a tridecapeptide which is thought to bind to receptors located on dopamine cells in the ventral tegmental area (VTA). Rats with cannulas implanted in the VTA showed a significant increase in time spent in an environment in which they had received bilateral injections of neurotensin on previous days. This is indicative of conditioned reinforcement in which the neuropeptide was the primary reinforcer. In order to determine the specificity of neurotensin receptor interactions, 3 fragments of the peptide were examined at 2 doses. NT1-8 and NT8-13 were found to be inactive while NT1-11 demonstrated significant activity. The results suggest that NT in the VTA is capable of inducing reinforcing effects. This is the first evidence for a non-opiate 'reward peptide'.

Animals↗
PubMed1984

Diminished amphetamine anorexia and enhanced fenfluramine anorexia after midbrain 6-hydroxydopamine.

Rats were made hyperphagic by 6-hydroxydopamine (6-OHDA) injected bilaterally into the ventral midbrain; then they were restricted to a 6 h/day feeding schedule and tested for appetite suppression with amphetamine and fenfluramine in randomized order. Amphetamine anorexia was diminished while fenfluramine anorexia was enhanced (both P less than 0.001). The opposite effect on fenfluramine anorexia shows that the effect of 6-OHDA on amphetamine anorexia was not due to hyperphagia masking the anorexia. Norepinephrine in the forebrain was 90% depleted, but DA and serotonin levels were within 9% of normal. These results demonstrate a new way to dissociate amphetamine and fenfluramine anorexia, as others have done with lateral hypothalamic lesions or DA depletion. The 6-OHDA injections, which were of a type that cause hyperphagia, apparently destroyed a substrate for amphetamine anorexia and also facilitated a substrate for fenfluramine anorexia.

Animals↗
PubMed1984

Endogenous opiate reward induced by an enkephalinase inhibitor, thiorphan, injected into the ventral midbrain.

Opiates are known to be reinforcing when injected into the ventral tegmental area (VTA). The present study produced conditioned reinforcement with local injections of exogenous d-ala2-met5-enkephalinamide (DALA), a potent analogue of met-enkephalin, and with thiorphan , an enkephalinase inhibitor which protects endogenous opiates from enzymic degradation. In a conditioned place preference paradigm, rats received injections of DALA (1.0, 3.0, or 8.0 micrograms), thiorphan (60 micrograms), and/or naloxone (10 micrograms), or saline vehicle. Conditioned reinforcement was obtained with 8.0 micrograms of DALA and also with thiorphan but not with thiorphan plus naloxone. This suggests that reward can be generated by endogenous opiates in the VTA. Tests during the light phase and dark phase suggested that diurnal periodicity may play a role in opiate reward. It is concluded that the VTA can generate conditioned reward through transmitter-receptor interaction involving an endogenous opiate substrate which is probably enkephalinergic.

Amino Acids, Sulfur↗
PubMed1983

Self-injection of amphetamine directly into the brain.

Rats learned to self-administer d-amphetamine (10 micrograms/microliter) through a cannula implanted in the nucleus accumbens. They responded more frequently for 65 +/- 15 nl of amphetamine than for equal amounts of saline. When presented with two levers (one amphetamine, one blank) they responded more on the correct lever for amphetamine. They would also switch levers, when necessary, to maintain access to the drug. When half the usual drug intake was given automatically, animals reduced their response rate by half, thus self-regulating the total amount of amphetamine they received. In tests for leakage into the ventricles, eight rats that self-injected with an accumbens cannula showed response extinction when switched to a ventricular cannula. We conclude that amphetamine self-injected into the accumbens is a positive reinforcer. This localization of 'amphetamine reward' suggests that the nucleus accumbens contains a synaptic mechanism underlying amphetamine abuse and, perhaps, also natural reinforcement of behavior.

Animals↗
PubMed1983

Amphetamine-induced hyperphagia and obesity caused by intraventricular or lateral hypothalamic injections in rats.

Overeating and obesity relative to controls was produced by multiple bilateral injections of 0.5 mg of amphetamine in the lateral ventricles of female rats eating a palatable, high fat diet. This behavioral and physiological rebound following the expected period of anorexia was accompanied by long-term depletion of dopamine in the striatum and of norepinephrine in the hypothalamus. This suggested the next experiment in which 50 micrograms of amphetamine were injected repeatedly in the lateral hypothalamus; again a brief period of anorexia was followed by hyperphagia and chronic obesity. This suggests that amphetamine acts in the lateral hypothalamus not only to suppress feeding, but in high doses it may also have local neurotoxic effects that cause an upward shift in body weight maintained by overeating.

Amphetamine↗
PubMed1982

Overeating after midbrain 6-hydroxydopamine: prevention by central injection of selective catecholamine reuptake blockers.

Earlier research from this laboratory showed that 6-hydroxydopamine (6-OHDA) injected into the ventral midbrain of rats causes overeating and the gradual development of obesity in association with extensive depletion of forebrain norepinephrine. It was proposed that depletion of norepinephrine or epinephrine was the cause of the behavioral abnormality. This was questioned on the basis of experiments showing that 6-OHDA can cause non-selective lesions and also that non-selective neurotoxins can cause hyperphagia. To help resolve this question, the present experiments used 191 rats in 28 groups to test 3 doses of 6-OHDA and 3 different pretreatments with reuptake blockers, amphetamine, desmethylimipramine and benztropine. The result of midbrain 6-OHDA alone was hyperphagia that was highly correlated with the dose. Pretreatment with intraperitoneal desmethylimipramine (DMI) caused gastric distress, and systemic amphetamine caused delayed overeating, but these unwanted side effects were avoided by injecting the drugs directly into the midbrain 15 min before the 6-OHDA. DMI and amphetamine partially prevented catecholamine depletion in the forebrain and totally prevented subsequent hyperphagia and obesity. Benztropine prevented dopamine depletion, but had no effect on hyperphagia. We conclude that some of the neurons protected by local injection of amphetamine and DMI are probably norepinephrine or epinephrine fibers that ascend through the ventral midbrain and have as one of their functions the inhibition of food intake. These neurons could also play a role in the control of body weight.

Animals↗
PubMed1979

Hyperphagia following intraventricular p-chlorophenylalanine-, leucine- or tryptophan-methyl esters: lack of correlation with whole brain serotonin levels.

The methylester hydrochlorides of DL-p-chlorophenylalanine (PCPA), L-leucine and L-tryptophan were intraventricularly administered to rats. All compounds produced increased food intake compared to saline administration. PCPA and leucine administration significantly decreased serotonin levels by 15--18%, while no serotonin depletion occurred following tryptophan injections. The data suggest that intraventricular injections of large quantities of neutral amino acid methyl esters may cause hyperphagia in rats through non-serotonergic effects on brain function.

Animals↗
PubMed1979

Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating.

This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.

Animals↗
PubMed1978

Effect of the anorectic drug, phenylpropanolamine, on blood glucose in rats.

Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The present study investigated the hypoglycemic effects of intraperitoneal PPA on rats to test the possibility that it might derive some of its anorectic properties through effects on glucostatic mechanisms. PPA tended to lower blood glucose levels in normal rats; the glycemia reducing effect was larger and statistically significant in rats made hyperglycemic by prior treatment with streptozocin to cause diabetes. This is the first evidence that PPA migh possibly reduce feeding by increasing blood sugar utilization.

Animals↗
PubMed1978

Three anorectic drugs: similar structures but different effects on brain and behavior.

Neurochemical probes are starting to tease apart several neurotransmitter systems that are involved in suppressing feeding. Instead of a classical medial hypothalamic lesion, neurotoxins or neurochemical inhibitors can be used to produced animal models of the obese. These models make it clear that amphetamine and fenfluramine do not act in the same way. In addition to actions on brain synapses, these drugs may act directly or indirectly on the receptors that monitor energy availability. Phenylpropanolamine (PPA) apparently has anorectic action within the lateral hypothalamus, but this could be due to a number of actions such as: (a) an adrenergic synaptic effect, (b) a direct receptor effect, (c) an indirect effect on glucoreceptors caused by increasing glucose utilization, or (d) some combination of these. In addition, these drugs taken systemically could activate similar mechanisms peripherally, thereby prompting a barrage of cues to and from the brain. Throughout this discussion it has been emphasized that the therapist who uses any of these drugs, needs to be aware of the possible changes in mood, behavior and physiological signs that are thought to occur in animals. Eventually the therapist will be able to take advantage of these side-effects to coordinate the drug's style with that of the patient.

Amphetamine↗
PubMed1977

Influence of p-chloroamphetamine on female sexual reflexes and brain monoamine levels.

The effect of p-chloroamphetamine(PCA) on female sexual reflexes was biphasic. Administration of PCA to receptive females initially terminated ongoing sexual behavior and this effect was correlated with the release of monoamines, particularly serotonin (5-HT). Sexual reflexes were abolished within 15 min of PCA injection. Other reflexes, including reciprocal forepaw treading, lateral head weaving, hindlimb abduction and Straub tail, were elicited by PCA. The long term infuence of PCA was the opposite. A facilitation of female sexual behavior occurred accompanied by a relatively specific depletion of 5-HT (10 mg/kg, 66% depletion; 20 mg/kg, 80% depletion) with both dopamine and norepinephrine depleted by less than 15%. This long term facilitation of female sexual reflexes was not blocked by dexamethazone suggesting that PCA was acting directly on the neural substrate for mating and did not produce it facilitation via adrenal progesterone. This biphasic infuence of PCA on mating reflexes, paralleling its effect on monoamine transmission, suggests serotonergic involvement in the integration of mating behavior.

Amphetamines↗
PubMed1976

Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorophenylalanine.

Loss of brain serotonin was associated with overeating and increased body weight. Rats injected with p-chlorophenylalanine intraventricularly began overeating after 3 days and continued to display marked hyperphagia, primarily in the daytime, accompanied by increased body weight for 1 to 2 weeks. The effect was related to drug dose and to the degree and duration of serotonin depletion. Norepinephrine and dopamine levels were not significantly affected. It is concluded that p-chlorophenylalanine disinhibits feeding, as it does a number of other behaviors, by depleting serotonin. This suggests that hypothalamic lesions or dietary deficiencies which selectively and sufficiently deplete serotonin would lead to overeating.

Animals↗