Relapse to cocaine-seeking after hippocampal theta burst stimulation

Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse).     

Directionality of rewarding impulses within the medial forebrain bundle self-stimulation system of the rat

Self-stimulation performance of rats was tested with conditioning pulses to the anterior preoptic area of the medial forebrain bundle followed at various intervals by test pulses to the contralateral posterior hypothalamic area of this bundle. Alternatively, conditioning pulses were delivered through the posterior electrode and test pulses were sent through the anterior electrode. The animals' performance in these two test sequences was indicative of (i) synaptic facilitation and (ii) a posterior convergence site of "self-stimulation impulses" in the medial forebrain bundle.     

Facilitation of brain self-stimulation by central administration of norepinephrine

Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin.     

Olfactory input to the hypothalamus: electrophysiological evidence

Electrical stimulation of the rat's olfactory bulb or lateral olfactory tract elicited unit discharges in the region of the medial forebrain bundle of the lateral hypothalamus, with latencies of 4 to 25 milliseconds. Unit responses in this area were driven by odors in preparations that were paralyzed to prevent breathing artifacts.     

Light-induced changes in pineal hydroxyindole-O-methyltransferase: abolition by lateral hypothalamic lesions

The activity of hydroxyindole-O-methyltransferase, the melatoninforming enzyme in the pineal gland, is several times greater in rats kept in continuous darkness than in those kept in continuous light. Lesions transecting the medial forebrain bundle in the lateral hypothalamus suppress these differences in enzyme activity and abolish light-induced changes in pineal weight. These findings indicate that the medial forebrain bundle may participate in the control of this enzymatic response to environmental lighting.     

Metabolic mapping of the brain during rewarding self-stimulation

Local rates of cerebral glucose utilization were measured in rats by the quantitative 2-deoxy-D-[14C]glucose autoradiographic method during electrical stimulation of the ventral tegmental area. Rats trained in intracranial self-stimulation showed a pattern of changes in forebrain metabolic activity distinctly different from the pattern seen in rats stimulated by the experimenter. These findings provide information about the distribution of local cerebral activity specific to reinforced instrumental behavior.     

Norepinephrine: reversal of anorexia in rats with lateral hypothalamic damage

Injection of norepinephrine in the lateral ventricles of rats recovering from lateral hypothalamic anorexia caused immediate feeding and, frequently, overeating. Intraventricular administration of the alpha-noradrenergic blocker, phentolamine, suppressed feeding in both normal rats and rats that had recovered from lateral hypothalamic lesions. Feeding is reinforced by ascending medial forebrain bundle fibers that form alpha-noradrenergic synapses in the hypothalamus and forebrain. Damage to these fibers suppresses feeding by reducing noradrenergic transmission and, hence, the rewarding value of food. Recovery of feeding after hypothalamic lesions coincides with the recovery of noradrenergic reward function.     

Neural pathways associated with hypothalamically elicited attach behavior in cats

Small electrolytic lesions were made in cats through electrodes, which, when stimulated, elicited either quiet biting attack or affective paw strike attack upon rats. The Nauta method for impregnating degenerating axoplasm was used to reveal that degeneration resulting from lesions at quiet attack sites followed largely along the course of the medial forebrain bundle, while the degeneration after lesions of affective attack sites was concentrated more heavily in the periventricular system.     

Distinct "feeding" and "hunger motivating" systems in the lateral hypothalamus of the rat

Electrodes were implanted in the middle hypothalamus of rats to determine the neural organization of the "feeding" centers. Stimulations of the farand midlateral hypothalamic area produced feeding responses in sated animals, but only the former caused sated animals to cross an electrified grill to press a lever for food. After lesions had been made in the medial forebrain bundle, however, stimulations in the far-lateral hypothalamic area resulted in feeding in sated animals but failure to cross the electrical barrier to press a lever for food. Simultaneous far-lateral and "satiety" center stimulations produced feeding in sated animals but failed to "motivate" grill-crossing behavior.     

Heart rate: differential effects of hypothalamic and septal self-stimulation

Heart rate in rats was recorded during self-stimulation with electrodes permanently implanted in both the hypothalamus and the septal region. Acceleration was observed during stimulation of the hypothalamus, and deceleration during stimulation of the septal region. In both areas self-stimulation reduced variability in heart rate.     

Vagotomy: effect on electrically elicited eating and self-stimulation in the lateral hypothalamus

A subdiaphragmatic vagotomy markedly inhibits eating and self-stimulation produced in rats by lateral hypothalamic stimulation. The stomach is known to be affected by hypothalamic stimulation via the vagus, and afferents from the stomach can influence the hypothalamus via the same nerve. Consequently, this result suggests that eating and self-stimulation may be partly controlled by hypothalamic influences on the stomach which, in turn, affects hypothalamic sensitivity.     

Analgesia from electrical stimulation in the brainstem of the rat

Stimulation at several mesencephalic and diencephalic sites abolished responsiveness to intense pain in rats while leaving responsiveness to other sensory modes relatively unaffected. The peripheral field of analgesia was usually restricted to one-half or to one quadrant of the body, and painful stimuli applied outside this field elicited a normal reaction. Analgesia outlasted stimulation by up to 5 minutes. Most electrode placements that produced analgesia also supported self-stimulation.One placement supported self-stimulation only in the presence of pain.     

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.     

Intracranial self-stimulation in man

Intracranial self-stimulation techniques, modified for use with neuropsychiatric patients, provide data suggestive of positive and negative reinforcing properties of brief electrical stimulation to various subcortical structures of the human brain.     

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.     

Estrous cycle in the rat: effects on self-stimulation behavior

The performance of female rats, in pressing a bar for electrical stimulation of the hypothalamus, changes during the estrous cycle. Highest barpressing rates accompany the appearance of vaginal cornification. This increase is not an artifact of increased spontaneous activity at estrus, although the factors underlying these changes in activity may also mediate the changes in self-stimulation behavior.     

Serotonin: release in the forebrain by stimulation of midbrain raphé

Electrical stimulation of the midbrain raphé, an area in which neuronal perikarya containing serotonin are aggregated, produces an increase in 5-hydroxyindoleacetic acid and a decrease in serotonin in the forebrain. These changes indicate that serotonin in the brain can be released via a specific neural pathway, namely, the system of axons projecting into the forebrain from serotonin-containing neurons in the midbrain raphé.     

Testosterone concentration in the male chick brain: an autoradiographic survey

Differential uptake of [(3)H]testosterone in male chick brain was found in periventricular areas of preoptic-hypothalamic continuum. Concentration of silver grains for all decapitation periods was especially high in the medial preoptic area, particularly the nucleus praeopticus paraventricularis magnocellularis. Distribution of testosterone-sensitive cells is in agreement with studies showing neuroanatomical control of reproductive behavior by the avian forebrain.     

Electrophysiological identification of a visual area in shark telencephalon

Optic nerve stimulation in the shark evokes short-latency telencephalic field potentials localized to the ipsilateral, posterior central nucleus. Such a well-defined visual area in elasmobranch telencephalon further challenges classical formulations of forebrain evolution. Moreover, its ipsilateral representation confirms recent evidence for a crossed thalamotelencephalic visual projection.