Cardiovascular classical conditioning in rabbits (Oryctolagus cuniculus) using appetitive or aversive hypothalamic stimulation as the US.

Examined the bar-press self-stimulation, shuttle-box preference, and cardiovascular classical conditioning of 2 groups of 6 male rabbits as a function of electrical stimulation of the medial or lateral hypothalamus. Results show that Ss having access to lateral hypothalamic stimulation bar-pressed to receive stimulation and made approach responses in the shuttle box. Ss having access to medial hypothalamic stimulation did not bar-press and made escape responses in the shuttle box. The cardiovascular UCRs of all Ss consisted of a blood-pressure increase and heart-rate decrease; CRs consisted of heart-rate decreases. Thus, while medial and lateral hypothalamic stimulation had different motivational properties, both provided effective UCSs for eliciting similar heart-rate CRs. Data indicate that cardiovascular changes elicited by hypothalamic stimulation are not merely global adjustments to aversive stimulation. (18 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement and suppression of self-stimulation after ventromedial hypothalamic lesions.

Investigated the effects of lesions in the ventromedial hypothalamus (VMH) upon self-stimulation in 25 male hooded Long-Evans rats. Ss trained to press a bar for lateral hypothalamic (LH) stimulation showed an enhancement of responding during the 1st 24 hrs after VMH lesioning, followed by a suppression of responding for several days. The degree of response suppression, but not enhancement, was correlated with an increase in food intake. In Ss trained to shuttle for LH stimulation, only the suppression effect was observed after VMH lesions. Barpressing for dorsal tegmental stimulation was not affected by the lesions. Results suggest that LH stimulation activates at least 2 groups of neurons: one group is specifically involved in barpressing and the other is involved equally in barpressing and shuttling. (French summary) (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age, side height, and spindle shape of the crib in climbing over the side

Norepinephrine (NE) was microinjected into the paraventricular nucleus (PVN), while microdialysis was used to monitor extracellular dopamine (DA) and acetylcholine (ACh) in the nucleus accumbens (NAc). The PVN is a site where exogenously administered NE can act through alpha 2 receptors to elicit eating behavior and preference for carbohydrates. It was hypothesized that NE in the PVN acts on a behavior reinforcement system by altering the DA/ACh balance in the NAc. NE microinjections (80 nmol in 0.3 microliter), which effectively elicited feeding in satiated rats in a separate test, caused a significant increase in extracellular DA (109%) and decrease in ACh (-27%) when the same animals were tested in the absence of food. In contrast when the food was available and ingested, ACh increased (51%) instead of decreasing. These results support the hypothesis that a functional link exists between the PVN and the NAc in which DA helps initiate and ACh helps stop appetitive behavior involved in the reinforcement of eating.     

Anatomical dissociation of the substrates of medial forebrain bundle self-stimulation and exploration.

The purpose of this research was to determine whether brain stimulation reward and exploration are induced by activation of the same set of neurons along the medial forebrain bundle. The behavioral version of the collision test was utilized with electrodes in the lateral hypothalamus (LH) and the ventral tegmental area (VTA). A collision effect obtained between LH and VTA in one behavior at the exclusion of the other was treated as evidence of the involvement of two different sets of fibers. In 4 rats, a collision effect was observed only in self-stimulation, whereas in 1 rat, a collision was obtained in exploration at the exclusion of self-stimulation. Three animals showed no collision in either behavior. These data suggest that coexistence of self-stimulation and exploration following medial forebrain bundle stimulation can be explained by current spread on two different sets of fibers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased ipsilateral expression of Fos following lateral hypothalamic self-stimulation

Immunohistochemical labeling of Fos protein was used to visualize neurons activated by rewarding stimulation of the lateral hypothalamic level of the medial forebrain bundle (MFB). Following training and stabilization of performance, seven rats were allowed to self-stimulate for 1 h prior to anesthesia and perfusion. Brains were then processed for immunohistochemistry. Two control subjects were trained and tested in an identical manner except that the stimulator was disconnected during the final 1 h test. Among the structures showing a greater density of labeled neurons on the stimulated side of the brains of the experimental subjects were the septum, lateral preoptic area (LPO), medial preoptic area, bed nucleus of the stria terminalis, substantia innominata (SI), and the lateral hypothalamus (LH). Several of these structures, the LPO, SI, and LH, have been implicated in MFB self-stimulation by the results of psychophysical, electrophysiological, and lesion studies.     

Lateral hypothalamic stimulation can augment or attenuate nucleus gigantocellularis escape: Evidence for appetite-associated aversion amelioration.

K. Carr and E. E. Coons (see PA, Vol 68:7638 and 3020) found that lateral hypothalamic (LH) stimulation ameliorates the aversiveness of stimulation of pain-implicated nucleus gigantocellularis (NGC), but this finding disagrees with other findings. To resolve this disagreement, we tested whether amelioration is differentially associated with the ability of LH stimulation to support self-stimultion (SS), to support responding to escape LH stimulation (LH escape), or to elicit stimulation-bound feeding (SBF). LH stimulation not yielding SBF always increased responding to escape from NGC stimulation (NGC escape) and was reward-escape in nature in supporting LH escape as well as SS. By contrast, LH stimulation yielding SBF always reduced NGC escape and was purely rewarding in that it only supported SS and never LH escape. In an additional experiment, the anxiolytic diazepam augmented the ability of LH stimulation yielding SBF to reduce NGC escape. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lipopolysaccharide, central in vivo biogenic amine variations, and anhedonia

Systemic administration of lipopolysaccharide (LPS), a non-specific activator of proinflammatory cytokine release from macrophages, provokes sickness characterized by anorexia, soporific effects, and disturbances of locomotor activity and exploration. In addition, endotoxin treatment may provoke an anhedonic response. Assessment of anhedonia in appetitive paradigms, however, is compromised by the anorexia provoked by the treatment. The present investigation assessed the anhedonic effects of LPS on rewarding lateral hypothalamic brain stimulation. Using a simultaneous discrimination, current titration procedure in the assessment of intracranial self-stimulation (ICSS), it was found that acute systemic administration of LPS (50 microg, 100 microg or 200 microg) reduced ICSS during the ascending sequence of current presentations, but had little effect on responding to a series of descending currents. In a parallel experiment, peripheral administration of LPS (100 microg) increased in vivo dopamine (DA) efflux from the nucleus accumbens, a region thought to be involved in goal-directed responding to positively reinforcing stimuli. It is suggested that LPS alters ICSS in a manner different than that observed following stressor exposure or peripheral IL-2 treatment. Furthermore, LPS may engender an anhedonic effect (possibly secondary to sickness), and the decline of responding reflects the relation between the cost of responding given in the face of sickness and the reward received for responding.     

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

In rats with perifornical lateral hypothalamic (LH) electrodes that induced feeding, self-stimulation through the same electrodes increased immediately after ventromedial hypothalamic (VMH) lesions and did not return to normal until food intake normalized and the rats had become obese. A unilateral far-LH lesion decreased feeding and contralateral perifornical LH self-stimulation. 6-hydroxydopamine (6-OHDA) injected into the midbrain to destroy the ventral noradrenergic bundle (VNAB) caused hyperphagia and increased LH self-stimulation. In summary, VMH or VNAB damage increased feeding and self-stimulation; contralateral far-LH damage decreased both. Results confirm the earlier suggestion that the VMH region is necessary for normal inhibition of feeding and feeding reward as reflected in self-stimulation rate. Although massive 6-OHDA-induced depletion of the dopamine system that passes through the LH can cause starvation and impair self-stimulation, results suggest that selective catecholamine depletion of ventral midbrain neurons with sparing of the A9 and A10 dopaminergic cells can disinhibit feeding and self-stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-stimulation of preoptic and lateral hypothalamus during behavioral thermoregulation in the albino rat.

Explored self-stimulating behavior in 5 male albino rats under ambient temperatures of 2, 12, 25, and 35.C while radiant-heat reinforcement was concurrently available. Preoptic self-stimulation was accompanied by hypothermia even at neutral temperatures, and in the cold, preoptic self-stimulation behavior was maintained alternating with the use of the heat-lamp lever. Conversely, self-stimulation of the lateral hypothalamus produced hyperthermia at neutral temperatures. In the cold, lateral hypothalamic self-stimulation was suppressed, although maintained sufficiently to preserve normal body temperatures without use of the heat lamp. High-temperature stress suppressed both preoptic and lateral hypothalamic self-stimulation. The interpretation suggests that electrical stimulation of the preoptic area signals a pseudowarmth state which results in activation of heat-loss mechanisms. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of dopamine in maintaining intracranial self-stimulation in the ventral tegmentum, nucleus accumbens, and medial prefrontal cortex.

Male albino Wistar rats were prepared with 2 chronic bipolar electrodes implanted ipsilaterally in the ventral tegmentum and either the nucleus accumbens or the medial prefrontal cortex. Once stable intracranial self-stimulation was elicited from both midbrain and forebrain electrodes, 6-hydroxydopamine lesions were placed into the ascending dopaminergic pathways between the rewarding electrode placements at the level of the lateral hypothalamus. Data suggest that dopamine plays an important role in self-stimulation in the ventral tegmentum and contributes to this behavior in the prefrontal cortex. Findings also show that nondopaminergic systems contribute to the phenomenon of brain-stimulation reward. (French summary) (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in self-stimulation at stimulation-bound eating and drinking sites in the lateral hypothalamus during food or water deprivation, glucoprivation, and intracellular or extracellular dehydration.

Examined the effects of hunger induced by food deprivation, 2-deoxy-{d}-glucose (200 mg/kg), or insulin (2 U/kg) and thirst induced by water deprivation, sodium chloride (4 M), or polyethylene glycol (5 ml of 30% w/w) on lateral hypothalamic self-stimulation in 40 male Long-Evans rats. Changes in self-stimulation were evaluated at electrodes that produced stimulation-bound eating and/or drinking or neither behavior. Daily 30-min test sessions consisted of 3 5-min periods of self-stimulation alternated with 3 5-min periods when barpresses resulted in 5-sec time-out from experimenter-delivered stimulation (stimulation escape). Food deprivation significantly increased self-stimulation; insulin, 2-deoxy-{d}-glucose, and sodium chloride significantly suppressed self-stimulation; water deprivation mildly inhibited self-stimulation; and polyethylene glycol had no effect. This pattern of findings was noted at electrodes that did and those that did not elicit eating and/or drinking. Findings do not support the hypothesis that the magnitude of lateral hypothalamic self-stimulation is differentially and predictably controlled by specific drive mechanisms indexed by the consummatory behaviors also elicited by the stimulation. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microbial degradation of tetraethyl lead in soil monitored by microcalorimetry

Fos immunohistochemistry was used to stain neurons in the caudal diencephalon, midbrain and hindbrain driven by rewarding stimulation of the lateral hypothalamus (LH). Increases in Fos-like immunoreactivity were most pronounced ipsilateral to the site of stimulation and tended to be confined within discrete structures such as the posterior LH, arcuate nucleus, ventral tegmental area (VTA), central gray, dorsal raphé, pedunculopontine area (PPTg), parabrachial nucleus, and locus coeruleus. At least two of these structures, the VTA and PPTg, have been implicated in medial forebrain bundle self-stimulation.     

Multiple knife cuts between the medial and lateral hypothalamus in the rat: A reevaluation of hypothalamic feeding circuitry.

In 2 experiments single or multiple sets of bilateral knife cuts were made in a total of 73 female CFE rats just lateral to the ventromedial hypothalamus (VMH) and/or just medial to the lateral hypothalmus (LH). The lateral VMH knife cuts by themselves produced greater hyperphagia and obesity than did the medial LH cuts. The lateral VMH knife cuts also significantly increased food intake and body weight in Ss previously given bilateral cuts along the medial LH border. Findings indicate that the feeding inhibitory fibers responsible for the hyperphagia syndrome do not project from the VMH to the LH, and this calls for a reevaluation of hypothalamic circuitry. It was also discovered that sham surgery in 7 Ss had a significant suppressive effect on the hyperphagia syndrome produced by hypothalamic knife cuts. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociable roles of dopamine within the core and medial shell of the nucleus accumbens in memory for objects and place.

There is increasing focus on the role of the nucleus accumbens (NAc) in learning and memory, but there is little consensus as to how the core and medial shell subregions of the NAc contribute to these processes. In the current experiments, we used spontaneous object recognition to test rats with 6-hydroxydopamine lesions targeted at the core or medial shell of the NAc on a familiarity discrimination task and a location discrimination task. In the object recognition variant, control animals were able to discriminate the novel object at both 24-hr and 5-min delay. However, in the lesion groups, performance was systematically related to dopamine (DA) levels in the core but not the shell. In the location recognition task, sham-operated animals readily detected the object displacement at test. In the lesion groups, performance impairment was systematically related to DA levels in the shell but not the core. These results suggest that dopamine function within distinct subregions of the NAc plays dissociable roles in the modulation of memory for objects and place. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin 5-HT2C agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens

In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c. ) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. A 5-HT2C selective agonist, 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212, 5 mg/kg, s.c.) also inhibited morphine-induced increases in extracellular DA concentrations in the NAc. Pretreatment of rats with the selective 5-HT2A antagonist, amperozide, had no effect on morphine-induced elevation of NAc DA concentrations. In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.     

Systemic morphine-induced Fos protein in the rat striatum and nucleus accumbens is regulated by mu opioid receptors in the substantia nigra and ventral tegmental area

To characterize how systemic morphine induces Fos protein in dorsomedial striatum and nucleus accumbens (NAc), we examined the role of receptors in striatum, substantia nigra (SN), and ventral tegmental area (VTA). Morphine injected into medial SN or into VTA of awake rats induced Fos in neurons in ipsilateral dorsomedial striatum and NAc. Morphine injected into lateral SN induced Fos in dorsolateral striatum and globus pallidus. The morphine infusions produced contralateral turning that was most prominent after lateral SN injections. Intranigral injections of [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO), a mu opioid receptor agonist, and of bicuculline, a GABAA receptor antagonist, induced Fos in ipsilateral striatum. Fos induction in dorsomedial striatum produced by systemic administration of morphine was blocked by (1) SN and VTA injections of the mu1 opioid antagonist naloxonazine and (2) striatal injections of either MK 801, an NMDA glutamate receptor antagonist, or SCH 23390, a D1 dopamine receptor antagonist. Fos induction in dorsomedial striatum and NAc after systemic administration of morphine seems to be mediated by dopamine neurons in medial SN and VTA that project to medial striatum and NAc, respectively. Systemic morphine is proposed to act on mu opioid receptors located on GABAergic interneurons in medial SN and VTA. Inhibition of these GABA interneurons disinhibits medial SN and VTA dopamine neurons, producing dopamine release in medial striatum and NAc. This activates D1 dopamine receptors and coupled with the coactivation of NMDA receptors possibly from cortical glutamate input induces Fos in striatal and NAc neurons. The modulation of target gene expression by Fos could influence addictive behavioral responses to opiates.     

Approach and withdrawal analysis of the effects of hypothalamic stimulation and lesions in rats.

Identified "purely" rewarding lateral hypothalamic and "purely" aversive medial hypothalamic electrodes in a paradigm in which Charles River male rats both initiated and terminated hypothalamic stimulation. Ss were then given a series of tests designed to assess the effects of brain stimulation on approach and withdrawal behaviors. Lateral hypothalamic stimulation facilitated approach behaviors and suppressed withdrawal behaviors, whereas medial hypothalamic stimulation produced largely the opposite effects. No serious motor deficits due to stimulation were detected with either type of electrode. In a 2nd experiment, the approach–withdrawal effects of bilateral lateral hypothalamic lesions were tested and found to suppress approach behaviors and facilitate withdrawal behaviors. Other neurological examinations revealed motor deficits, but these did not account for the specific pattern of results observed on the approach–withdrawal test. These approach–withdrawal phenomena are interpreted in terms of altering a natural balance between approach and withdrawal behavior facilitating systems in the lateral and medial hypothalamus, respectively. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural basis of stimulus-bound locomotor activity in the rat.

Stimulated lateral hypothalamic sites in male hooded rats. Locomotor activity was elicited in 9 Ss which supported self-stimulation and stimulus-bound motivational behavior. Results of 4 experiments show that this kind of locomotor activity (a) was elicited through directly excited neurons with absolute refractory periods in the range .75-1.1 msec.; (b) accumulated during stimulation and decays gradually after the end of stimulation; (c) had a magnitude dependent on the number of brief trains of stimulation applied; and (d) was not elicited by nucleus accumbens stimulation. Neuronal activity in a brainstem arousal system excited by the lateral hypothalamic situation showed the same 4 characteristics. Because of the comparability of these electrophysiological and behavioral characteristics, it is concluded that activity in the brainstem arousal system at least partly mediates the stimulus-bound locomotor activity. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of amphetamine and food deprivation on self-stimulation of the lateral hypothalamus and medial frontal cortex.

Intracranial self-stimulation of the lateral hypothalamus in 5 male Sprague-Dawley rats was markedly increased by subcutaneous dextroamphetamine administration and by food deprivation. In contrast, similar self-stimulation response rates obtained in the same Ss from the medial frontal cortex were unaffected by food deprivation and only slightly increased by dextroamphetamine administration. Furthermore, a large difference between dextro- vs levoamphetamine on response rate was obtained for lateral hypothalamic but not for medial frontal cortex self-stimulation. Results are consistent with a noradrenergic self-stimulation system for the lateral hypothalamus. Medial frontal cortex self-stimulation, however, appears to be mediated by a neuroanatomical and neurochemical system different from that of the lateral hypothalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuated Dopamine Efflux in the Rat Nucleus Accumbens During Successive Negative Contrast.

Rats shifted from 4% to 32% sucrose displayed successive negative contrast by initiating significantly fewer bouts of licking than control rats maintained on 4% sucrose. No significant increase in dopamine (DA) efflux in the nucleus accumbens (NAc) was observed during consumption of 4% sucrose by rats shifted from 32%. In contrast, consumption of 4% sucrose by control rats was accompanied by a significant increase in DA efflux in the NAc, which remained elevated 10 min postconsumption. These data are consistent with the hypothesis that DA efflux in the NAc reflects the current incentive valence of sucrose reward and its influence on initiation of individual bouts of sucrose consumption. (PsycINFO Database Record (c) 2010 APA, all rights reserved)