Sensorimotor functions of the striatopallidal system and lateral hypothalamus and consummatory behavior in rats.
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The effects of fluoxetine, a relatively selective long-acting serotonin uptake inhibitor, on the consumption of alcoholic and nonalcoholic drinks, cigarette smoking, and body weight were assessed in 29 men who were early stage problem drinkers. After a 2-week baseline, subjects were randomly assigned to receive 40 mg/day fluoxetine (n = 8), 60 mg/day fluoxetine (n = 11), or placebo (n = 10) for 4 weeks. Fluoxetine 60 mg/day decreased mean daily alcoholic drinks from (X +/- SEM) 8.3 +/- 0.7 during baseline to 6.9 +/- 0.7 and decreased total drinks per 14 days from 115.8 +/- 9.3 to 96.5 +/- 9.5 (p less than 0.01; 17.3% decrease from baseline), with no significant increase in days of abstinence. Neither 40 mg/day fluoxetine nor placebo had effects on intake of alcohol. Fluoxetine 60 mg/day decreased total and mean daily alcoholic drinks compared with 40 mg/day fluoxetine (ANCOVA, both p less than 0.02), but neither dose of fluoxetine was different from placebo. Compared with placebo, both 40 mg/day fluoxetine and 60 mg/day fluoxetine no differences were detected between treatment groups, 60 mg/day fluoxetine increased mean daily nonalcoholic beverages from baseline (5.0 +/- 0.4 to 5.6 +/- 0.3, p less than 0.01) and increased daily cigarettes smoked (from 25.1 +/- 4.6 to 26.9 +/- 4.5, p less than 0.05), whereas no significant changes from baseline were observed with 40 mg/day fluoxetine or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Animal studies suggest that angiotensin-converting enzyme inhibitors decrease alcohol intake. In a double-blind crossover study 42 normotensive alcoholics (36 men and six women) aged 24 to 65 years, consuming 8.2 +/- 2.3 (mean +/- SD) standard alcoholic drinks per day, were randomized to enalapril, 10 mg/day (n = 20) or 20 mg/day (n = 22), and placebo for 4 weeks. They monitored their daily alcohol intake and attended biweekly assessments, but no other treatment or advice was given. Compliance and alcohol intake were verified objectively. Mean daily alcoholic drinks were not significantly different during 10 mg/day enalapril (mean +/- SEM, 7.5 +/- 0.5), and its placebo (7.2 +/- 0.5), but both decreased from baseline (8.1 +/- 0.5; both p less than 0.05). Similarly, mean daily drinks during 20 mg/day enalapril (6.8 +/- 0.6) and its placebo (7.2 +/- 0.4) was not significantly different, but both were lower than baseline (8.3 +/- 0.5; both p less than 0.01). Fourteen (64%) of the patients taking 20 mg/day enalapril decreased alcohol intake from placebo by an average of 21% (range, 1.6% to 78.3%). Self-ratings of interest, desire, craving, and liking for alcohol also decreased from baseline during enalapril and placebo treatments, but the effects of both were similar. Plasma renin activity increased, compared with placebo, after 10 mg/day enalapril (from 0.3 +/- 0.2 [mean +/- SD] to 1.9 +/- 1.5 ng/L/sec) and after 20 mg/day enalapril (from 0.4 +/- 0.3 to 2.8 +/- 4.0 ng/L/sec) (both p less than 0.05). Blood pressure decreased within a normotensive range, compared with placebo, with 10 mg/day enalapril (by 6.0 and 8.5 mm Hg systolic and diastolic blood pressures) and 20 mg/day enalapril (by 7.7 and 5.0 mm Hg, respectively). Side effects were few and mild. No patient characteristic or drug effect correlated with changes in alcohol intake. There were no significant variations in nonalcoholic beverages, cigarette smoking, or body weight. These results indicate that enalapril does not alter alcohol intake in normotensive alcoholics with normal plasma renin activity. Studies with higher doses of enalapril in humans may be limited by increased frequency and severity of side effects.
Depression, eating disorders, and carbohydrate craving are frequently seen in alcoholics or recovering alcoholics. Accordingly, these disorders may share some mediating pathways. It is now well-established that there is a genetic predisposition to alcoholism. Through genetic means, our laboratory has developed an animal model of alcoholism. Free-fed Wistar rats were selectively bred for the traits of alcohol-preference (the P line) and non-preference (the NP line). After more than 20 generations of selection, the lines show a stable difference of more than six-fold in voluntary ethanol consumption. We have now shown that the P line satisfies all the perceived requirements of an animal model of alcoholism. One major discovered difference between the P and the NP line is the lowered content of serotonin in certain brain regions of the P rats. Interestingly, fluoxetine curbs the alcohol-seeking behavior of the P rats; variation in the carbohydrate content of the diet, however, does not modify voluntary ethanol intake. The P rats are similar in body weight to the NP rats, but are more active in a novel environment than the NP rats.
Peptide histidine isoleucine (PHI) and VIP are derived from the same precursor. While central VIP decreases food intake, potential effects of PHI on feeding have not been studied. In the current study, we found that PHI administered intracerebroventricularly (ICV) or into the hypothalamic paraventricular nucleus (PVN) or central nucleus of the amygdala (CeA) decreased food consumption in overnight-deprived rats. The magnitude of an anorexigenic response to PHI differed depending on the injection route: ICV-infused peptide evoked the most potent effect. We determined that that only PVN- and CeA-injected PHI did not have aversive consequences. In addition, we infused anorexigenic doses of PHI via the same routes and assessed Fos immunoreactivity of PVN oxytocin (OT) and vasopressin (VP) neurons using double immunohistochemistry. OT and VP are thought to promote feeding termination. PHI increased the percentage of Fos-positive OT neurons regardless of the injection route. PVN- and ICV-infused PHI induced activation of VP cells. We conclude that central PHI has an inhibitory influence on food intake in rats. The PVN, with OT and VP neurons, and CeA may be involved in the mediation of anorexigenic effects of PHI.
Leumorphin is a 29-amino-acid peptide derived from preproenkephalin B. Intracerebroventricular (i.c.v.) injection of leumorphin through an implanted cannula into the lateral ventricle of rats dose-dependently inhibited water intake induced by water deprivation, angiotensin II (AII) and carbachol. This effect was partially reversed by intraperitoneal injection of naloxone, an opiate antagonist. Naloxone alone rather attenuated water intake. The antidipsogenic effect of leumorphin was very potent: 0.6 pmol of the peptide significantly inhibited AII-induced drinking. Dynorphin 1-17 was almost as potent as leumorphin in inhibiting drinking, whereas alpha-neo-endorphin and leucine-enkephalin (Leu-enkephalin) were far less effective. Leumorphin given i.c.v. dose-dependently enhanced eating and this effect was abolished by naloxone. Dynorphin was as potent as leumorphin in inducing feeding, whereas alpha-neo-endorphin and Leu-enkephalin had no significant activity when 6 nmol was used. General activity measured by an Automex was enhanced by i.c.v. injection of leumorphin but required larger amounts of the peptide than did drinking behavior. The very potent and specific effects of leumorphin and dynorphin on drinking behavior suggest that the antidipsogenic activity of these peptides is of physiological significance like their effect on feeding.
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Drinking is increased by prior exposure to lithium-conditioned stimuli. Experiment 1 showed that this phenomenon is not an artifact of testing subjects with a novel, palatable drinking fluid and also showed that lithium-conditioned olfactory stimuli produce a biphasic change in drinking, with drinking suppressed at the start of exposure to the conditioned stimulus (CS) and enhanced a long time after CS onset or exposure. Experiment 2 showed that the increased drinking aftereffect of lithium-conditioned stimuli is not a result of the instrumental reinforcement of the drinking response by the scheduling of water access following drug injections during conditioning, and Experiments 3, 4, and 5 showed that the increased drinking effect occurs even if subjects are injected with lithium prior to the test session. The results of Experiments 3 and 5 alos showed that lithium administration and exposure to lithium-conditioned stimuli have independent and opposite aftereffects: Lithium disrupts drinking, whereas prior exposure to lithium-conditioned stimuli increases consumption. The relevance of conditioned opponent and compensatory processes to the findings is discussed.
Exposure to taste or spatial cues previously paired with lithium administration resulted in more drinking during a test session started 15 min. later than did exposure to stimuli previously presented in the absence of drug treatment (Experiments 1, 2, 4, and 5). This outcome reflected an elevation of intake above baseline levels (Experiment 1) and required the presence of the lithium-paired cues rather than merely a history of lithium injections (Experiments 1, 2, 4, and 5). The increased drinking was evident in tests with novel (Experiments 1, 4, and 5) as well as familiar (Experiment 2) palatable solutions and was not attributable to a greater degree of thirst in subjects exposed to the lithium-predictive cues (Experiments 4 and 5). The phenomenon was attenuated by extinction of the lithium-conditioned stimuli (Experiment 3). However, the increased drinking aftereffect probably was not a result of the conditioned aversiveness of lithium-predictive cues, since shock-conditioned stimuli did not elicit enhanced consumption (Experiment 5). Various explanations of the effect are discussed.
BACKGROUND: Because of the amphetamines' abuse potential and capability of exacerbating or inducing mood and psychotic disturbances, investigations of the behavioral effects of amphetamines commonly involve non-human animals, with the laboratory rat being by far the most common species used. Although investigators of the behavioral effects of amphetamine in rats sometimes refer to doses used as being "low", "moderate", "high", etc., it is not clear in what sense these terms apply. OBJECTIVES: To develop an operational definition of a low dose of amphetamine in rats, we reviewed studies that assessed the behavioral effects of dextroamphetamine (d-AMP) in rats in which some subset of doses, administered SC, IM or IP, was described as being "low". We then used the results of these studies to establish what the lowest effective dose ranges were across a variety of behavioral domains and compared these doses and their effects with those obtained with normal, healthy adult humans. RESULTS: While the range of the lowest doses used in the studies with rats was quite broad (0.025-2.0 mg/kg), the median lowest effective doses observed (in the studies using doses of 0.125 mg/kg or less) were between 0.125 and 0.165 mg/kg across the behavioral domains of consummatory behavior, unconditioned or spontaneous behavior, learned behavior, and drug discriminative control. This range of doses was also found to be comparable to the lowest behaviorally effective doses of d-AMP (SC or PO) in normal human adults, which suggests that the sensitivity to the behavioral effects of amphetamine in these two species is fairly comparable. CONCLUSIONS: Because of their ability to alter a wide variety of behaviors in rats, we conclude that low doses of d-AMP are in the 0.1-0.4 mg/kg range. Doses within this range typically: 1) constitute the ED50 in most drug discrimination/generalization procedures; 2) increase a variety of consummatory behaviors; 3) increase a variety of unconditioned or spontaneous motor activities; 4) increase low rate schedule-controlled behavior while exerting variable effects on high rate schedule controlled behavior; and 5) improve performance on some choice tasks, particularly those requiring sustained attention. Our analyses also indicate that, with respect to behavior, investigators do not always agree on what constitutes a low dose of amphetamine in rats and that doses assumed to be low for this species often are relatively high.
The entire sequence of feeding behavior patterns exhibited by intact and anosmic channel catfish to food extracts was also released by single amino acids. L-arginine (> 10(-6) M), L-alanine (> 10(-6) M), and L-proline (> 10(-4) M) were each highly effective at releasing consummatory behavior patterns, such as turning, increasing pumping of water across the gill arches, and biting-snapping. Swallowing required solid objects, whereas rhythmic movement of the hyoid was released by > 10(-2) M L-arginine alone. For the biting-snapping behavior, the number of bites depended upon both the number of eddies containing the amino acid above the behavioral threshold concentration and the amino acid applied. Multiple eddies of > 10(-3) M L-proline and L-alanine provoked up to 25 bites per test; however, the most effective stimulus for releasing biting-snapping behavior at low concentrations was L-arginine (behavioral threshold 3 x 10(-7) M). In comparison to 10(-4) M L-alanine and L-arginine, other amino acids were less effective stimuli.
A dopamine D1 (SKF-38393, 1 mg)- or D2 (LY-171555, 0.1 mg)-receptor agonist inhibited intake of an intraorally infused solution of sucrose by male rats, a test of consummatory ingestive behavior. Treatment with a D1 (SCH-39166, 0.1 mg) or D2 (raclopride, 0.6 mg) antagonist reversed inhibition by the respective agonist but enhanced the inhibitory effect of cholecystokinin octapeptide (CCK-8; 1.8 micrograms). It was not possible to demonstrate specific effects of D1 and D2 agonists on intake of pellets, a test that does not discriminate consummatory ingestive behavior from appetitive ingestive behavior, i.e., behavior used to obtain food. The results demonstrate specific involvement of dopamine D1 and D2 receptors in inhibition of consummatory ingestive behavior.
Pyramidal cells in the CA1 hippocampal region displayed transient network oscillations (200 hertz) during behavioral immobility, consummatory behaviors, and slow-wave sleep. Simultaneous, multisite recordings revealed temporal and spatial coherence of neuronal activity during population oscillations. Participating pyramidal cells discharged at a rate lower than the frequency of the population oscillation, and their action potentials were phase locked to the negative phase of the simultaneously recorded oscillatory field potentials. In contrast, interneurons discharged at population frequency during the field oscillations. Thus, synchronous output of cooperating CA1 pyramidal cells may serve to induce synaptic enhancement in target structures of the hippocampus.
Cats with pontile lesions, frontal neocortical lesions, and thyroidectomized cats display a dissociation of the appetitive and consummatory components of grooming behavior following tactile stimulation of the body surface, an abnormal behavior which waxes and wanes with the seasons of the year. Tryptophan hydroxylase activity and serotonin levels were significantly decreased in the superior colliculi (but not other brain regions) in cats with pontile lesions or frontal neocortical lesions, but not in thyroidectomized cats. Systemic administration of 5-hydroxytryptophan or monoamine oxidase inhibition plus tryptophan administration abolishes the abnormal grooming behavior in each group of cats, and microinjections of 5-hydroxytryptophan or serotonin into the superior colliculi has the same effect, indicating that the change in a serotonergic system is a critical aspect of the abnormal behavior in cats with lesions and that a serotonergic system may also be involved in the genesis of the abnormal grooming behavior in thyroidectomized cats. Functional inactivation of the serotonergic system by p-chlorophenylalanine, LSD, or serotonin receptor blockade does not induce the abnormal grooming behavior in normal cats, indicating that other factors are involved. Cats with lesions and thyroidectomized cats display a rhythmic dysfunction in the excretion of glucocorticoids and glucocorticoid administration abolishes the abnormal grooming behavior, suggesting that glucocorticoids are the other critical factor. Adrenalectomized cats do not display the abnormal grooming behavior, but when adrenalectomized cats are treated with p-chlorophenylalanine, the abnormal behavior appears. Thus, a serotonergic system in the superior colliculi, operating at some level of glucocorticoid function, is involved in the integration of appetitive and consummatory grooming behaviors.
Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of times the rats visit a bottle filled with sucrose (appetitive behavior). In this study, we investigated if the suppression of consummatory behavior was dependent upon the increase of appetitive behavior. The shift from consummatory to appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to the sucrose solution in the bottle. However, the intraoral intake of the sucrose solution was still decreased in NPY-treated rats. NPY did not modify taste reactivity as measured by aversive responses during continuous intraoral infusion of sucrose or ingestive and aversive responses to brief intraoral infusion of sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a bottle and intake from the bottle and inhibited sexual behavior in male rats but had no effect on the sexual behavior in the absence of a bottle. The visits and the intake were suppressed, but sexual behavior was not activated by adding QHCl (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior, therefore, does not indiscriminately facilitate consummatory behavior. Male rats showed aversive or ingestive behavior and sexual behavior simultaneously during intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases intraoral intake and increases appetitive ingestive behavior via partially separable mechanisms that are independent of taste aversion.
Theoretical models of animal and human sexual behavior have evolved from two very different literatures, yet they contain many common behavioral components that may reflect the action of similar neuroendocrine and neurochemical systems. The study of animal sexual behavior has been largely concerned with mechanisms that underlie the pattern of consummatory behaviors observed during copulation, behaviors that tend to be highly stereotyped, sexually differentiated, and species-specific. There are important species differences in the behavioral topography, endocrine control, and neural substrates of consummatory behaviors, which tend to be extreme when comparing animals and humans. Although this has led to an increased interest in comparative animal behavior, it has also helped to foster a general perception that animals and humans are fundamentally different. In contrast to consummatory behaviors, appetitive behaviors (which serve to bring animals and humans into contact with sexual incentives) are more flexible, less sexually differentiated, and less species-specific and span a variety of situations other than sexual interactions. Appetitive behaviors are thus viewed as "sexually specific" when they are displayed under sexual circumstances and reinforced by sexual incentives. Interestingly, an appetitive/consummatory dichotomy has emerged in the human literature which distinguishes measures of sexual desire or arousal from "performance" measures of masturbation or copulation. In fact, sexual desire, which reflects fantasy and behavioral excitement, has been further differentiated from sexual arousal, which reflects genital blood flow. The present analysis attempts to pull together these seemingly disparate literatures into a coherent theoretical framework that emphasizes similarities and differences in the structure of sexual behavior across rats and humans.
In the sea hare, Aplysia californica, consummatory feeding behavior is selectively abolished by bilateral crushes of the cerebral-buccal connectives and recovers by postlesion day 13. Recovered biting responses are initially weak and increase in magnitude gradually with time. The lesions do not affect appetitive feeding behavior or unrelated reflexive behaviors. Thus, feeding in Aplysia can be used to examine the neural basis of behavioral recovery after CNS injury.
Traditional intake measures of voluntary consumption of food or fluid from a specific location involve both appetitive and consummatory behaviors. Appetitive behaviors are food finding behaviors displayed by an animal prior to the consumption of the food, whereas consummatory behaviors are the behaviors involved in the actual consumption of the food. Intraoral intake of a fluid can be measured by directly infusing it into the oral cavity of an animal and quantifying the consummatory behaviors. The present study compared the effects of immune activation (lipopolysaccharide, LPS) and toxin (lithium chloride, LiCl)-induced changes on both a traditional intake measure (bottle drinking) and an intraoral intake measure. In Experiment 1, rats were injected intraperitoneally with LPS (200 microg/kg), LiCl (0.15 M, 20 ml/kg) or NaCl vehicle, and voluntary sucrose (0.3 M) intake was monitored for 1 h from a graduated drinking tube. Voluntary intake was again assessed on a second test day, 72 h later under the same conditions. In Experiment 2, a continuous intraoral infusion of sucrose (0.3 M) was given via intraoral cannulae following systemic injections of LPS, LiCl or NaCl vehicle on two different test days, 72 h apart. Rats injected with LiCl displayed reduced sucrose intake on both the voluntary intake measure and the intraoral intake measure relative to controls (P's<.05). The reduced intake observed was of greater magnitude on the second test day of both experiments, consistent with conditioning effects. In contrast, LPS reduced sucrose intake only when assessed with the traditional intake measure. Intraoral sucrose intake remained unchanged relative to controls. The present results provide further evidence that activation of the immune system has adverse effects on the appetitive phase of ingestion, whereas the consummatory aspects are unaffected.