What psychological process mediates feeding evoked by electrical stimulation of the lateral hypothalamus?

Because electrical stimulation of the lateral hypothalamus (ESLH) can elicit both feeding and reward, most investigators have concluded that stimulation does not evoke the aversive cues associated with hunger. It has been hypothesized, instead, that ESLH primes ingestion by evoking pleasurable taste sensations. A direct taste of this hedonic hypothesis was undertaken in rats that showed stimulus-bound feeding. Contrary to the prediction, it was found that the taste reactions (gapes, tongue protrusions, etc.) during ESLH were more aversive than hedonic. It is suggested that the stimulation influences behavior by potentiating the salience, but not the hedonic value, of external stimuli. The advantages of this incentive salience hypothesis are that it circumvents the need to postulate a hedonic sensory experience during stimulation and that it can explain how evoked feeding may switch to other behaviors when conditions are altered.

Convulsions may alter the specificity of kappa-opiate receptors.

Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that electroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.

The propensity for nonregulatory ingestive behavior is related to differences in dopamine systems: behavioral and biochemical evidence.

Previous research has shown that animals predisposed to eat and drink in response to electrical stimulation of the lateral hypothalamus (ESLH) are similarly predisposed to drink excessively when tested for schedule-induced polydipsia. The eating and drinking elicited by both experimental paradigms appears to be unrelated to homeostatic need and has been called nonregulatory ingestive behavior. In this study, the relation between properties of dopaminergic neural systems and the predisposition to exhibit nonregulatory ingestive behavior was investigated. It was found that rats that eat and drink during ESLH show greater behavioral sensitization to a series of amphetamine injections that those that do not exhibit ingestive behavior during ESLH. In addition, footshock stress produced a greater increase in forebrain dopamine utilization in rats that engaged in nonregulatory ingestive behavior. This evidence is consistent with the hypothesis that there are individual differences in the responsiveness of forebrain dopamine systems that are related to the behavioral predisposition to exhibit nonregulatory ingestive behavior.

Unilateral substantia nigra lesions and schedule-induced polydipsia.

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) on schedule-induced polydipsia (SIP). Lesions were made in either the "dominant" or "non-dominant" hemisphere as defined by an amphetamine rotation test. It was found that unilateral lesions of either the "dominant" or "non-dominant" SN significantly reduced SIP and also significantly impaired somatosensory responsiveness as indicated by the "tactile extinction test." Somatosensory neglect was significantly greater following a lesion in the "dominant" hemisphere than "non-dominant" hemisphere.

Individual differences in non-regulatory ingestive behavior and catecholamine systems.

Animals that eat and/or drink in response to electrical stimulation of the lateral hypothalamus (ESLH-pos) are more responsive to both schedule-induced polydipsia (SIP) tests and a series of amphetamine (AMPH) injections than animals that do not exhibit these behaviors (ESLH-neg). Moreover, prior exposure to the behaviorally activating SIP experience, or to AMPH, permanently transformed the ESLH-neg animals into animals that reliably ate or drank during ESLH. Prior treatment with AMPH also increases the water consumed during subsequent SIP tests. Thus, initial of induced differences in sensitivity to activating experiences can determine behavioral propensities.

Changes in responsiveness to mu and kappa opiates following a series of convulsions.

After a series of seven electroconvulsive shocks, mice (C57BL/6J) showed a marked change in their response to opiates. Although very large doses of mu agonists induce convulsions in normal control mice, our evidence indicated that this was accomplished through nonopiate mechanisms: they could not be blocked by naltrexone and the pattern of drug potencies (codeine greater than morphine greater than levorphanol) was not consistent with an opiate response. In contrast, after electroconvulsive shock small doses of mu agonists induced convulsions that could be blocked by naltrexone and the pattern of drug potency (levorphanol greater than morphine greater than codeine) was consistent with an opiate mechanism. Kappa drugs, on the other hand, produced convulsions in both control and ECS animals, although there was an enhanced responsiveness in the latter. Furthermore, the convulsions produced by kappa drugs were blocked by naltrexone and showed stereoselectivity in both control and ECS animals. The changes in responsiveness to mu and kappa opiates cannot be explained on the basis of a general increase in seizure susceptibility, as sensitivity to the nonopiate convulsant, strychnine, was not enhanced after electroconvulsive shock. The results point to a qualitative change in response to mu agonists after electroconvulsive shock, but only a change in sensitivity to kappa agonists.

Asymmetry in the effects of unilateral 6-OHDA lesions on eating and drinking evoked by hypothalamic stimulation.

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the caudate nucleus and nucleus accumbens on eating and drinking evoked by electrical stimulation of the lateral hypothalamus (ESLH). Lesions were made on either the 'dominant' or 'non-dominant' hemisphere as defined by an amphetamine-rotation test. We report here that lesions of the 'dominant hemisphere' were significantly more effective in disrupting ESLH-evoked behavior as well as producing longer-lasting deficits in somatosensory responsiveness as measured by the 'tactile extinction test'.

Morphine responsiveness and seizure proneness.

Previous research demonstrated that following amygdala kindling, animals showed a heightened sensitivity to morphine's convulsive effects and an exaggerated Straub tail response. These effects were evident to 3 months after their last convulsion and could be blocked by naloxone pretreatment. The present paper extends these findings by demonstrating that animals given metrazol or electroshock (ECS) convulsions also showed an enhanced morphine response that was blocked by naltrexone. Both metrazol- and ECS-treated animals convulsed in response to doses of morphine that produced little or no effect in control animals. In addition, it was shown that brain damage induced by electrode implantation or neocortex penetration by skull screws also increased an animal's sensitivity to morphine even in the absence of prior convulsions. This effect, however, could not be blocked by naltrexone. Finally, as opiate receptors vary with the diurnal rhythm, we determined that following amygdala kindling, animals are more sensitive to morphine's convulsive action during their dark phase when receptor number and sensitivity are highest. The results indicated that seizure proneness, whether induced by a history of prior convulsions or brain damage, increased sensitivity to morphine. This effect may be due to a change in opiate receptors only when prior convulsions have occurred.

Ingestive behavior evoked by hypothalamic stimulation and schedule-induced polydipsia are related.

Some, but not all, rats eat or drink in response to electrical stimulation of the lateral hypothalamus. Similarly, some, but not all, rats given food intermittently display schedule-induced polydipsia. In this experiment, animals that ate or drank during electrical stimulation tended also to be those displaying polydipsia. Thus, individual differences in predisposition to engage in ingestive behavior are consistent under two very different conditions.

Lateral hypothalamic stimulation: stimulus-bound eating and self-deprivation.

Research was undertaken in an attempt to clarify the relationship between stimulus-bound eating and self-deprivation produced by electrical stimulation of the lateral hypothalamus. It was hypothesized that if these two phenomena are mediated through a common population of feeding-related neurons, a significant correlation should be observed between these two behaviors. No significant relationship was discovered among the rats tested for both stimulus-bound eating and self-deprivation. Although this finding by itself does not rule out some role for feeding-related neural elements in stimulus-bound eating and self-deprivation, the present results provide no support for this view and suggest alternative explanations should be sought.

An inability of gamma-acetylenic GABA to block eating evoked by hypothalamic stimulation.

Several lines of evidence have implicated the nigrostriatal dopamine system and the neocortex for eating occurring either spontaneously or in response to electrical stimulation of the lateral hypothalamus (ESLH). GABA-ergic neural systems are known to modulate activity in the nigrostriatal system and neocortex. The GABA-transaminase inhibitor, gamma-acetylenic GABA (GAG) was administered to rats eating in response to ESLH. This drug produced hypersynchronization of the cortical EEG and behavioral sedation, but did not alter the current threshold for evoking eating by ESLH. Implications of results for understanding mechanisms underlying ESLH-induced eating are discussed.

Amygdaloid kindling and the GABA system.

The effect of increased brain GABA levels on fully kindled amygdala seizures was investigated in Long-Evans rats. The newly synthesized GABA-transaminase inhibitor, gamma-acetylenic GABA (GAG) administered on four consecutive days (100 mg/kg, followed by 50 mg/kg, i.p.) was found to either significantly reduce, or eliminate entirely, the behavioral seizures normally produced by amygdala stimulation. The effect is seen after the first injection of GAG although its magnitude was greater on subsequent days. Behavioral seizures reappeared 2 to 3 days after termination of GAG treatment. The duration of electrographic seizures (self-sustained amygdala after discharge) was either unchanged or greater on the first day of GAG treatment, but was briefer on subsequent days. The duration of afterdischarges returned to normal levels 1 to 2 days earlier than the behavioral seizures after the termination of GAG. Picrotoxin (1.5-2 mg/kg, i.p.) did not antagonize either electrographic or behavioral effects of inhibition produced with GAG. Electrical stimulation of amygdala delivered during the initial sedation stage induced by picrotoxin resulted in further regression of kindled seizures in the majority of animals. Although in doses employed, GAG alleviates amygdaloid-kindled seizures its use requires caution in view of its ability to reduce arousal level.

Individual differences in aggressiveness of female hamsters: response to intact and castrated males and to females.

The aggressive behaviour of female hamsters was studied while they were housed in large enclosures with males and in brief tests with males or females. Some females are not aggressive with any male, whereas others are very aggressive toward all males in both testing conditions. Females that are not aggressive toward intact males may be very aggressive toward castrated males or females. When the animals are housed together for long periods of time, males dominate only if they are much heavier. Male dominance takes a relatively long time to establish and often there is an equivocal period characterized by reversals of dominance. Female dominance is rapidly established. Unless the male is much heavier, the female determines the presence or absence of agonistic behaviour.

Another hamster paradox: more males carry pups and fewer kill and cannibalize young than do females.

The response of virgin male and female golden hamsters to young was studied. In contrast to most species, males are more likely to carry pups than are females. All males carried pups, but approximately 50% of females cannibalized the young. The females that did not cannibalize the pups carried them with less hesitation and after shorter latencies than did the males. The response of females to young was not correlated with the aggressiveness displayed toward adult males during separate tests. Tests with gonadectomized females indicated that the maintenance of pup-killing behavior is not dependent on concurrent gonadal hormones. Progesterone injections did not significantly increase pup killing in males that had previously carried young. Speculations on the adaptive significance of the male and female hamster's response to pups are presented.