Discrimination by rats of conspecific odors of reward and nonreward

The hypothesis that, after receiving reward and nonreward, rats excrete differential odors perceptible to other rats was tested by making the correct turn in a T-maze contingent on discrimination of any such odors. Clear evidence for an "odor of nonreward or frustration" was obtained, and there was the suggestion of a transistory odor after early reward trials.     

Hypothalamic reward mechanism: two first-stage fiber populations with a cholinergic component

Refractory periods were estimated for fibers of the hypothalamic substrate of brain stimulation reward. Two nonoverlapping populations were evident: a homogeneous fast population and a more heterogeneous slow population. Cholinergic blockade eliminated the contribution of the fast but not the slow fibers, while dopaminergic blockade reduced responding without significantly influencing either directly activated fiber population. These data indicate that the hypothalamic reward substrate is more complex than has been widely appreciated; it contains two or more parallel subsystems, and one of these subsystems has a cholinergic link.     

Modulation of brain reward circuitry by leptin

Leptin, a hormone secreted by fat cells, suppresses food intake and promotes weight loss. To assess the action of this hormone on brain reward circuitry, changes in the rewarding effect of lateral hypothalamic stimulation were measured after leptin administration. At five stimulation sites near the fornix, the effectiveness of the rewarding electrical stimulation was enhanced by chronic food restriction and attenuated by intracerebroventricular infusion of leptin. In contrast, the rewarding effect of stimulating neighboring sites was insensitive to chronic food restriction and was enhanced by leptin in three of four cases. These opposing effects of leptin may mirror complementary changes in the rewarding effects of feeding and of competing behaviors.     

Intracranial self-stimulation and wakefulness: effect of manipulating ambient brain catecholamines

Rats were given disulfiram, an inhibitor of norepinephrine biosynthesis, to see if norepinephrine is a transmitter for motivation in electrical stimulation of the brain. Animals given the drug paused in bar pressing, appearing asleep or sedated; if replaced on the bar, they always resumed pressing at normal rates. The decrease in bar pressing may result from a direct or indirect effect of the drug on wakefulness rather than on reward.     

Complementary process to response bias in the centromedian nucleus of the thalamus

Activity in several areas of the human brain and the monkey brain increases when a subject anticipates events associated with a reward, implicating a role for bias of decision and action. However, in real life, events do not always appear as expected, and we must choose an undesirable action. More than half of the neurons in the monkey centromedian (CM) thalamus were selectively activated when a small-reward action was required but a large-reward option was anticipated. Electrical stimulation of the CM after a large-reward action request substituted a brisk performance with a sluggish performance. These results suggest involvement of the CM in a mechanism complementary to decision and action bias.     

Neuronal activity related to reward value and motivation in primate frontal cortex

In several areas of the macaque brain, neurons fire during delayed-response tasks at a rate determined by the value of the reward expected at the end of the trial. The activity of these neurons might be related to the value of the expected reward or to the degree of motivation induced by expectation of the reward. We describe results indicating that the nature of reward-dependent activity varies across areas. Neuronal activity in orbitofrontal cortex represents the value of the expected reward, whereas neuronal activity in premotor cortex reflects the degree of motivation.     

"Copulation-reward site" in the posterior hypothalamus

Posterior hypothalamic selfstimulation of male rats, in which monopolar,platinum electrodes had been belaterally implanted, increased after systdmic injection of testosterone. constant stimulation to the same site elicited immediate copulation with estrous female rats. During constant stimulation males would press a bar to open a door for access to females. Even after ejaculation, males continued to open the door and to display sexual activity until stimulation terminated. Posterior hypothalamic stimulation is like normal sexual stimulation; it is rewarding, the reward varies with the amount of the sex hormone, and it elicits motivated copulation.     

BOLD responses reflecting dopaminergic signals in the human ventral tegmental area

Current theories hypothesize that dopamine neuronal firing encodes reward prediction errors. Although studies in nonhuman species provide direct support for this theory, functional magnetic resonance imaging (fMRI) studies in humans have focused on brain areas targeted by dopamine neurons [ventral striatum (VStr)] rather than on brainstem dopaminergic nuclei [ventral tegmental area (VTA) and substantia nigra]. We used fMRI tailored to directly image the brainstem. When primary rewards were used in an experiment, the VTA blood oxygen level-dependent (BOLD) response reflected a positive reward prediction error, whereas the VStr encoded positive and negative reward prediction errors. When monetary gains and losses were used, VTA BOLD responses reflected positive reward prediction errors modulated by the probability of winning. We detected no significant VTA BOLD response to nonrewarding events.     

Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward

Norepinephrine (NE) is widely implicated in opiate withdrawal, but much less is known about its role in opiate-induced locomotion and reward. In mice lacking dopamine beta-hydroxylase (DBH), an enzyme critical for NE synthesis, we found that NE was necessary for morphine-induced conditioned place preference (CPP; a measure of reward) and locomotion. These deficits were rescued by systemic NE restoration. Viral restoration of DBH expression in the nucleus tractus solitarius, but not in the locus coeruleus, restored CPP for morphine. Morphine-induced locomotion was partially restored by DBH expression in either brain region. These data suggest that NE signaling by the nucleus tractus solitarius is necessary for morphine reward.     

Schedules of irrelevant signals and maintenance of monitoring behavior

Subjects clearly discriminated between critical and irrelevant signals, yet an intermittent schedule of irrelevant signals produced reliably higher rates of responding than did the continuous presentation of such signals. This is exactly the result obtained with similar variations in reward schedules. It seems that essentially "meaningless" changes in stimulation can reinforce behavior, too.     

Temporal summation and refractoriness in hypothalamic reward neurons as measured by self-stimulation behavior

A neurophysiological technique of double-pulse stimulation has been applied to freely moving rats with chronic indwelling electrodes in the hypothalamic reward area. Self-stimulation thresholds, measured as a function of the interpulse interval, generated curves with time constants characteristic of refractory periods and temporal synaptic summation. The results indicate a way of studying central neuronal processes for which the overt behavior of the animal is the dependent variable.     

Possible etiology of schizophrenia: progressive damage to the noradrenergic reward system by 6-hydroxydopamine

Single or repeated intraventricular injections of 6-hydroxydopamine caused marked and long-lasting deficits in brain self-stimulation and other rewarded behaviors in the rat. The behavioral deficits, as well as the depletion of brain norepinephrine induced by 6-hydroxydopamine, were prevented by prior treatment with chlorpromazine. Episodic or continuous formation of endogenous 6-hydroxydopamine in man as a result of a genetically determined enzymatic error could selectively damage the binding capacity and, eventually, the structural integrity of the noradrenergic reward mechanism. Such damage might cause the fundamental symptoms and long-term downhill course of schizophrenia.     

Operant behavior changes norepinephrine metabolism in rat brain

Rats performing a lever-pressing response for water reward in an operant situation, when compared with control groups, showed an increase in brain norepinephrine metabolism. One control group included rats which were handled and deprived of water in the same way as the experimental group but were not trained to perform the operant task. We conclude that performance in an operant situation affects norepinephrine metabolism.     

Surgery in the rat during electrical analgesia induced by focal brain stimulation

Chronic monopolar electrodes were implanted in the region of the midbrain central gray in eight rats. In three rats, continuous 60 cycle-per-second sine-wave stimulation resulted in an electrical analgesia defined by the elimination of responses to aversive stimulation while general motor responsiveness was retained. Exploratory laparotomy was carried out in these animals during continuous brain stimulation without the use of chemical anesthetics. Following surgery, brain stimulation was terminated, and responses to aversive stimuli returned. Electrodes effective in inducing electrical analgesia at the lowest currents were located at the dorsolateral perimeter of the midbrain central gray. It was concluded that focal brain stimulation in this region can induce analgesia in the absence of diffusely applied "whole brain" stimulation.     

Electrical stimulation of the amygdala as a conditioned stimulus in a bait-shyness paradigm

Animals receiving low-intensity electrical stimulation of the basolateral nucleus of the amygdala while drinking plain tap water were injected with toxic doses of lithium chloride to examine whether brain stimulation can serve as a conditioned stimulus in a bait-shyness paradigm. Subjects receiving this pairing greatly reduced their water intake in a retention test, in a similar manner to a group in which saccharin was paired with poisoning. Pairing lithium chloride with stimulation of the amygdala had no effect on subsequent water intake in the absence of brain stimulation. This effect appears to be locus specific, as caudate stimulation could not serve as a conditioned stimulus.     

Closed-loop control of epilepsy by transcranial electrical stimulation

Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients.     

Biochemical transfer of relational responding (transposition)

Hooded rats were trained to choose the larger of two circles in order to obtain a liquid reward. Recipients of brain extract from these trained donors showed a significant preference for an even larger circle when given a nonreinforced test for several days after the injection of extract. The substrate for relational learning may be biochemically transferred.     

TEST OF DEUTSCH'S DRIVE-DECAY THEORY OF REWARDING SELF-STIMULATION OF THE BRAIN

Deutsch's theory of intracranial self-stimulation generates experimental predictions regarding the effects of both free stimulation of the brain and the pre-extinction training procedure on extinction behavior after rewarding stimulation of the brain. The results of one experiment confirmed the prediction regarding free stimulation; the other experiment did not provide the expected result. We concluded that Deutsch's theory, in its present form, is of restricted enerality.     

Escape from self-produced rates of brain stimulation

Rats were allowed to self-stimulate while their responses were being recorded on tape. Subsequently, prerecorded patterns of their brain stimulation were "played back" to them. All subjects learned to escape brain stimulation delivered in exactly the same manner as they had previously elected to receive it.     

Discrimination of tones during reinforcing brain stimulation

Hungry animals were trained to press a lever for brain stimulation. Different tones were presented concurrently with the stimulation. A second lever delivered food only during critical tone periods. Animals were able to discriminate tones presented concurrently with rewarding intracranial stimulation, and they also interrupted self-stimulation behavior to respond appropriately under other reinforcements.