Elliot S. Valenstein

Sexual Receptivity: Facilitation by Medial Preoptic Lesions in Female Rats

Lesions in the medial preoptic area of ovariectomized female rats reduced the quantity of estrogen needed to induce sexual receptivity in these animals. In addition, the number of days over which receptive behavior could be elicited after a single initial estrogen injection and with subsequent daily progesterone treatment was significantly increased by lesions in the medial preoptic area. These findings support the view that estrogen acts to reduce an inhibitory action that is tonically exerted by the medial preoptic area on pathways mediating estrous behavior.

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.

Individual behavioral responses to hypothalamic stimulation persist despite destruction of tissue surrounding electrode tip.

Abstract Behavior evoked by hypothalamic stimulation differs among animals, although their electrode placements appear histologically to be identical. These differences have been attributed to selective activation of functionally discrete neural circuits that are in close proximity. We report here, however, that in rats initially exhibiting “stimulus-bound” drinking, this behavior persists following either a series of progressively larger lesions, or a single large lesion, around the electrode tips. Similar results were obtained in rats afforded minimal stimulation experience prior to the lesions. These results suggest that individual differences in response to hypothalamic stimulation cannot be attributed solely to variations in the neuroanatomical locus of stimulation.

Amygdaloid kindling and the GABA system.

Summary: The effect of increased brain GABA levels on fully kindled amygdala seizures was investigated in Long‐Evans rats. The newly synthesized GABA‐transaminase inhibitor, ‐γ‐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.

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.

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.

Individual differences in sexual responsiveness to estrogen and progesterone in ovariectomized rats

Individual differences among 83 ovariectomized rats in behavioral responsiveness to estrogen were measured by scoring the quality of sexual receptivity induced by injections of estradiol benzoate (EB) and progesterone (P). The P dose remained constant but the quantity of EB administered was systematically reduced over successive weeks until lordosis behavior could no longer be elicited. This EB dose was considered threshold. This sequence of weekly hormone injections and receptivity tests was repeated to assess the reliability of our procedures. Animals had thresholds of either 2.0, 1.0 or 0.5 μg/kg EB on both tests; the correlation between threshold values on the two tests was high (r=0.66; p<0.001). Sixty-two females were used to determine the facilitating effects of various quantities of P following EB treatment. Subgroups were tested after the E alone and again after one of 6 P doses. Zero, 20, 50 and 100 μg P failed to elevate receptivity scores significantly; both 250 and 500 μg P had significant facilitating effects. The results demonstrated that individual differences in EB sensitivity can be measured reliably, and a further analysis also suggests similar individual differences in P responsiveness. Our threshold determination procedures provide a useful technique for measuring the effects of various experimental manipulations on the hormone sensitivity of brain mechanisms which regulate estrous behavior.

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.

Channeling of responses elicited by hypothalamic stimulation

SCIENTIFIC discovery, like mining, often progresses on a discontinuous course. Progress in one direction continues until a point of diminishing returns is reached. A new strike may produce a scurry of activity in another direction. The development of different techniques may prompt the reopening of a closed shaft. Only after a period of such exploration may a more complete picture of the field emerge. The history of the hypothalamus seems to be following such a course. Prior to the turn of this century, little attention was given to the hypothalamus. The fact that the obesity observed as part of the Friihlich syndrome was attributed to pituitary difficulties and not related to hypothalamic involvement clearly reflected the prevailing scientific bias. ANDERSON’ traced the history of this period and quoted the following portion of Friihlich’s remarks in 1940 at a symposium on the hypothalamus : “The discussions that I have attended the past two days have established the fact that we were wrong in 1901, that it was not the pituitary body but the hypothalamus, but then I must remind you that all we knew at that time was that the hypothalamus was an anatomical region lying beneath the thalamus. That is all we knew.” Following the classic work by KARPLUS and KREIDL,~ RANSON~~~ and his colleagues, and HESS,~~~ the hypothalamus became increasingly stressed as a significant area for the expression of emotion and motivated behavior. The fact that electrical stimulation in this region elicited a number of autonomic responses constituted a major portion of the evidence. Earlier reports emphasized the elicitation of isolated responses such as pupillary dilation and constriction, but there was a gradual awareness that stimulation was capable of activating integrated bodily changes characteristic of such states as rage, temperature regulation, eating and somnolence. For a brief period it was claimed that stimulation activated only the motor aspects of these states and not the motivational or affective components;7 however, later work demonstrated that the behavior elicited by hypothalamic stimulation had many properties in common with behavior motivated by more

Hormonal induction of behavioral estrus modified by electrical stimulation of hypothalamus

Abstract Sexual receptivity was induced by sequential injections of estrogen and progesterone in ovariectomized female rats which had bilateral, monopolar electrodes permanently implanted into either the medial preoptic area (MPOA) or the medial basal hypothalamus (MBH). Intermittent electrical stimulation of the MPOA during the first 6 hours of estrogen priming significantly reduced the intensity of estrous behavior measured 2 days later. Comparable stimulation of the MBH produced a non-significant increase in receptivity. The use of electrical stimulation to study the ways in which hormones affect central sites of action is discussed.