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Using signaled barpressing tasks to study the neural substrates of appetitive and aversive learning in rats: behavioral manipulations and cerebellar lesions.

The development of standard within-subject conditioning tasks for studying similarities and differences in the neural substrates of appetitive and aversive learning is described. Rats learned to press a bar during a brief tone presentation to receive a food pellet reward (the appetitive task). Using the same tone signal, conditioning chamber, and trial timing parameters, the same rats were then trained to press the bar during the tone presentation to avoid a mild footshock (the aversive task). As an initial study of the neural substrates of these forms of learning, the involvement of the cerebellum was assessed. Bilateral lesions of the deep cerebellar nuclei prevented the learning of the aversive task but had no effect on the learning of the appetitive task.

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Application of antisense DNA method for the study of molecular bases of brain function and behavior.

The antisense DNA method has been used successfully not only in vitro but also with in vivo systems to block effectively the expression of specific genes. An increasing number of studies have shown that antisense DNA administered directly into the brain can modify various kinds of behaviors. These findings strongly suggest that the antisense DNA method can be widely used as a powerful tool for the study of the molecular bases of behavior. In addition to traditional methods of behavioral genetics, the antisense DNA method may provide a new approach for the study of the effects of gene in behavioral function. In this article, we review recent studies reporting in vivo effects of antisense DNA on brain function and behavior.

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Hypothalamic and extrahypothalamic substrates of predatory attack. Suppression and the influence of hunger.

Electrical stimulation of medial hypothalamic and ventromedial hypothalamic areas of the cat brain stops the initiation of spontaneous predatory attack in cats, confirming similar evidence of other investigators. Furthermore, a new attack suppressing area, the mammillary bodies, was uncovered. Facilitation of predatory attack by hunger raised the electrical threshold for attack in the mammillary bodies. In addition, baseline levels of neural activity in attack suppressing brain areas prior to any brain stimulation were found to decrease when the cats were hungry and killing was facilitated and neural activity increased when the cats were on ad lib. feeding. These data support the hypothesis that modulation of excitability of neural systems functioning to suppress is involved in facilitation of attack behavior by hunger.

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Effects of sibutramine on the appetitive and consummatory aspects of feeding in non-human primates.

This study examined how sibutramine (0.06-4.0 mg/kg, i.m.), a clinically effective weight-loss medication which increases extracellular serotonin and norepinephrine levels, affected the appetitive and consummatory aspects of feeding of non-human primates. The effects were compared to the effects of the positive control dexfenfluramine (2.0-6.0 mg/kg, p.o.), which primarily increases extracellular serotonin levels. Baboons had access to food 24 h each day, but they had to complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Sibutramine increased the latency to the first meal of the session in females, and decreased consummatory behavior without affecting other appetitive behavior in males and females. In contrast, dexfenfluramine, increased the latency to the first meal of the session, and decreased both appetitive and consummatory behavior in males and females. The behavioral mechanism by which sibutramine decreases food intake is distinct from other anorectic drugs, including dexfenfluramine, that have been tested in this paradigm.

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Brainstem lesions and gustatory function: I. The role of the nucleus of the solitary tract during a brief intake test in rats.

Using an automated gustometer, licking behavior in rats was evaluated for a range of concentrations of appetitive and aversive stimuli in rats following electrolytic lesions in the rostral nucleus of the solitary tract (NST). Lesions of the NST flattened the concentration-response function for all gustatory stimuli. They attenuated the concentration-response function for MgCl2, QHCI, and NH(4)Cl by shifting it to the right by 0.5 log unit, attenuated the function for citric acid and Polycose by shifting it to the right by 1.5 log units, and fully eliminated the function for sucrose and NaCl. This failure to respond appropriately, however, was specific to gustatory stimuli because all rats reduced ingestive responding when presented with increasing concentrations of capsaicin, a trigeminal stimulus. Together, the data show that the NST is critical for responding appropriately to changes in intensity of a gustatory, but not a trigeminal, stimulus.

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Oxytocin inhibits food and fluid intake in rats.

Increasing evidence indirectly suggests a role for oxytocinergic neurons in the control of ingestive behaviors. The present study was aimed at directly investigating a possible effect of oxytocin on food and water intake in rats. Oxytocin, whether administered intracerebroventricularly (ICV) (1-10 micrograms/rat) or intraperitoneally (IP) (375-3,000 micrograms/kg) dose dependently inhibited food intake in freely feeding animals; in schedule-fed animals fasting for 21 h, oxytocin not only reduced food intake but also reduced the time spent eating and increased the latency to first meal. On the other hand, oxytocin antagonist d(CH2)5Tyr(Me)-[Orn8]-vasotocin, ICV injected at the dose of 10 micrograms/rat, increased food intake and time spent eating and reduced the latency to first meal; moreover, it completely prevented the effect of oxytocin. Water intake was studied both in freely drinking animals and in three different models of thirst (water deprivation, hypertonic saline administration, angiotensin II injection). In all cases, oxytocin dose dependently inhibited water intake, in a dose range of 0.1-10 micrograms/rat (ICV) or 93-750 micrograms/kg (IP). In the water deprivation model, ICV pretreatment with d(CH2)5Tyr(Me)-[Orn8]-vasotocin completely prevented the antidipsogenic effect of oxytocin. In conclusion, these data show that oxytocin directly inhibits food and water intake in rats, the effect being specifically mediated by brain oxytocin receptors. This may support the idea that the brain oxytocinergic system plays an important role in the regulation of ingestive behaviors.

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