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Post-training intracranial self-stimulation facilitates a hippocampus-dependent task.

Previous research has shown that post-training intracranial self-stimulation facilitates implicit or procedural memory. To know whether it can also facilitate explicit memory, post-training intracranial self-stimulation was given to Wistar rats immediately after every daily session of a delayed spatial alternation task that seems to depend on the integrity of the hippocampal memory system. We tested the effects of intracranial self-stimulation in three consecutive learning phases which tried to make the task progressively more difficult: 10 s delay (D10 phase), 30 s delay (D30 phase), and inverting the starting position of the animals to make their response more dependent on allocentric cues (INV phase). Every phase finished when each rat achieved a fixed learning criterion. Intracranial self-stimulation facilitated the flexible expression of the learned response (INV phase). That is, when the starting position was randomly inverted, only the rats that received intracranial self-stimulation maintained the performance level acquired in the previous training phases. Changing the starting position reduced the correct performance of the non-treated subjects, which need more training sessions to achieve the learning criterion and made less correct responses than treated rats. These findings show that post-training intracranial self-stimulation can facilitate hippocampus-dependent memories.

Animals↗

Facilitation of self-stimulation of ventral tegmentum by microinjection of opioid receptor subtype agonists.

Intracranial self-stimulation (ICSS) evoked from the ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) was assessed following microinjections of mu (Tyr-D-Ala2-N-Me-Phe4-Gly5ol: DAGO), delta-(D-Ala2, D-Met5)-enkephalin: DADME) or kappa (Dynorphin-B or Rimorphin) opioid receptor subtype agonists or saline into either VTA-SN or LH-MFB. The current intensity was fixed at an optimum level to obtain 60-70% of the maximum asymptotic response rate. DAGO (5 micrograms/0.5 microliters), DADME (2 micrograms/0.5 microliters) or Dynorphin B (0.5 microgram/0.5 microliters) injected into VTA-SN facilitated the self-stimulation rates of VTA-SN by 27%, 32%, and 59%, respectively. These microinjections did not alter the self-stimulation of LH-MFB when effects of these injections were still persisting in VTA-SN. Similar doses of these opioid receptor agonists injected into LH-MFB had no significant effect on the self-stimulation rates of either LH-MFB or VTA-SN. The facilitatory effects of DADME were completely abolished by naloxone (30 mg/kg IP). Taken together, these results suggest that all three opioid receptor subtypes of ventral tegmentum and not of lateral hypothalamus are involved in the electrically evoked self-stimulation of VTA-SN.

Analgesics↗

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.

Brain↗

Relation of rat brain acetylcholine levels to duration of self-stimulation and escape behavior.

Total brain acetylcholine (ACh) was assayed in groups of animals after various periods of operant responding maintained by electrical stimulation of the lateral posterior hypothalamus or of escape behavior induced by electrical stimulation of the midbrain tegmentum. Different groups of trained rats were placed in identical Skinner boxes for periods of 1 to 24 hr. The following groups were studied: controls, self-stimulators receiving electrical stimulation, escapers from brain stimulation or peripherally applied aversive stimulation, self-stimulators not receiving electrical stimulation prior to decapitation, tubocurarine-paralyzed respired rats with electrodes in the posterior-lateral hypothalamus not receiving stimulation, and a group of tubocurarine-paralyzed, respired rats receiving electrical stimulation automatically. It was found that brain stimulation decreased total brain ACh, regardless of whether the stimulation was positive, as during self-stimulation behavior, or negative, as during escape behavior. Animals that receivied positive stimulation while being paralyzed showed similar decreases in total brain ACh, but the change in ACh was smaller. No changes occurred in animals that were paralyzed that recieved no electrical stimulation. It is concluded that brain usage produced by electrical stimulation of discrete functional pathways causes a reduction of total ACh, but this is unrelated to the specific motivational properties of the electrical stimuli.

Acetylcholine↗

Differential hypothalamic self-stimulation behaviour in Roman high-avoidance and low-avoidance rats.

Monopolar electrodes were implanted bilaterally and symmetrically into a small well defined region of the posterior lateral hypothalamus in 11 rats of the selected strains Roman high-avoidance (RHA/Verh, 6 animals) and Roman low-avoidance (RLA/Verh, 5 animals). Intracranial electrical stimulation (ICS) was used to study possible strain difference with respect to self-stimulation behaviour. Using a shuttle-box, the experimental set-up allowed measurements of the animal's preference, aversion, neutrality or ambivalence towards the stimulus. For both rat strains 10 electrode sites were tested with identical stimulation currents (100-600 microA in increments of 100 microA). Significant differences between the selected strains were found for preference (self-stimulation) and aversion: RLA/Verh-rats showed self-stimulation at lower stimulation currents than RHA/Verh-rats. At higher currents, both strains showed similar self-stimulation performance. RLA/Verh-rats escaped more often from ICS yielding self-stimulation at five of the six current levels. It is concluded that, in comparison with the RHA strain, RLA/Verh-rats are more sensitive to aversive effect of lateral hypothalamic stimulation. This seems to be associated with an increased sensitivity to the rewarding effects of such stimulation.

Animals↗

Amygdaloid self-stimulation: a movable electrode mapping study.

The distribution of electrical self-stimulation foci within the amygdala (AMY) was mapped using movable electrodes in rats. Each barpress delivered a 0.4-s train of cathodal rectangular pulses of fixed intensity and duration and variable frequency. The rate-frequency function was recorded for successive dorsoventral sites. Self-stimulation was found throughout the AMY, except in the lateral nucleus. Depending on the site, maximum rates varied from 3 to 37 barpresses/min, whereas threshold frequencies varied from 9.2 to 40 pulses/train; no correlation between these two aspects of self-stimulation was found. Most threshold frequencies lay within the range of 10 to 20 pulses/train, which suggests a relatively homogeneous distribution of rewarding efficacy within the positive areas. The lowest threshold estimates are comparable to those usually obtained for pontine and medial forebrain bundle areas, which suggests that the AMY is an important focus for self-stimulation.

Amygdala↗

Neurotensin participates in self-stimulation of the medial prefrontal cortex in the rat.

The effects of intracerebral microinjections of neurotensin and xenopsin on self-stimulation of the medial prefrontal cortex of the rat were studied. Unilateral microinjections into the medial prefrontal cortex of neurotensin at doses of 0.625, 1.25, 2.5, 5 and 10 nmol produced a dose-related decrease of self-stimulation in the ipsilateral medial prefrontal cortex. Self-stimulation of the contralateral medial prefrontal contex, used as control, was not affected by the microinjections. Similar results were found with the neurotension-like octapeptide, xenopsin. Unilateral microinjections of xenoposin into the medial prefrontal cortex, at doses of 1.8, 3.6, 7.2 and 14.4 nmol produced a dose-related decrease of self-stimulation of the ipsilateral medial prefrontal cortex. Self-stimulation of the contralateral medial prefrontal cortex was not affected. These results suggest that neurotensin is part of the neurochemical substrate of self-stimulation in this cortical area.

Animals↗

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. In a second experiment a unilateral far-LH lesion decreased both feeding and contralateral perifornical LH self-stimulation. In Experiment 3, 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. These 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, the 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. In all three experiments LH self-stimulation and food intake covaried, which suggests that they are functionally related.

Animals↗

Cardiovascular reactions from hypothalamic self-stimulation in the rat.

Arterial blood pressure (BP) and heart rate (HR) were continuously recorded during lateral hypothalamic self-stimulation with optimal stimulus parameters in rats. Hyper-hypotensive, hypertensive and hypotensive reactions were observed during separate self-stimulation, and the biphasic type considerably prevailed over other types of reactions. During the single cycles of self-stimulation hyper-hypotensive and hypertensive reactions with different heart rate reactions also occurred. In this case the biphasic type was seen in 75% of all reactions, whereas the hypotensive type occurred in 25% of the cases. The main type of BP reaction (92%) during continuous self-stimulation for 60-240 min was a gradual increase of the mean BP level from 15 to 40 mm Hg against initial values (p less than 0.001), that depended on the duration of self-stimulation. Changes of HR were more variable: tachycardia and bradycardia were seen approximately with the same frequency. Comparative analysis of cardiovascular reactions during hypothalamic SS and escape reactions provoked by ventromedial hypothalamus stimulation revealed some peculiarities of autonomic manifestations during positive and negative emotional reactions. The results of this comparison raises the question of a stress-reaction during self-stimulation behaviour.

Animals↗

'Complete' spinal cord injury does not block perceptual responses to genital self-stimulation in women.

BACKGROUND: A priori hypothesis: vaginal and/or cervical self-stimulation will not produce perceptual responses in women with "complete" spinal cord injury (SCI) at or above the highest level of entry of the hypogastric nerves (T10-12) but will produce perceptual responses if SCI is below T-10. DESIGN: Women with complete SCI were assigned to a group with "upper" (T-10 and/or above) (n = 6) or "lower" (below T-10) (n = 10) SCI; uninjured women (n = 5) constituted a control group. Perceptual response to vaginal and/or cervical self-stimulation was quantified as magnitude of analgesia to calibrated finger compressive force. SETTING: Rutgers, The State University of New Jersey, Human Physiology Laboratory, College of Nursing, Newark. PARTICIPANTS: Consecutive samples of first 16 of 34 women with SCI who responded to nationwide advertisements, met inclusion criteria, and volunteered; control group was the first 5 respondents. INTERVENTION: Vaginal or cervical (cervix uteri) self-stimulation applied for 12 minutes, interspersed with non-stimulation periods, while measuring analgesia. MAIN OUTCOME MEASURE: Quantify analgesia magnitude to vaginal or cervical self-stimulation. RESULTS: Significant analgesia was produced in the uninjured group and the group with lower SCI, supporting the hypothesis. Unexpectedly, significant analgesia was also produced in the group with upper SCI. Women in the group with upper SCI also experienced menstrual discomfort, awareness of vaginal and/or cervical stimulation per se, and orgasms. CONCLUSIONS: (1) Genitospinal visceral afferent pathways function in the women in the group with upper SCI, although unrecognized by the American Spinal Injury Association criteria, and/or (2) there exists a functional genital afferent pathway that bypasses the spinal cord and projects directly to the brain, which we propose to be via the vagus nerves.

Adult↗

The effect of somatostatin on self-stimulation behavior in atropine- and methysergide-pretreated rats.

The effect of somatostatin on lateral hypothalamic self-stimulation was investigated in atropine- and methysergide-pretreated rats. Somatostatin markedly decreased the self-stimulation rate of the animals. Atropine in a dose which had no action on self-stimulation partly antagonized the effect of somatostatin. Methysergide potentiated the somatostatin-induced depression of self-stimulation behavior. These results suggest that the central cholinergic and serotoninergic systems may play a role in the somatostatin-induced inhibition of self-stimulation.

Animals↗

Vulnerability to stressor-induced disturbances in self-stimulation from the dorsal and ventral A10 area: differential effects of intraventricular D-Ala2-Met5-enkephalinamide, D-Ala2, N-Me-Phe4, Gly-Ol5-enkephalin, and D-Pen2, D-Pen5-enkephalin administration.

D-Ala2-Met5-enkephalinamide (DALA) (1.0 microg/microl) was administered intraventricularly to mice responding for electrical stimulation from the dorsal or ventral aspects of the VTA immediately prior to footshock (Experiment 1). Predictably, footshock reduced self-stimulation from the dorsal but not the ventral VTA immediately, 24, and 168 h following the stressor. Intraventricular DALA administration effected a partial attenuation of stressor-induced self-stimulation reductions from the dorsal VTA immediately and 24 h poststressor. Deficits appeared among DALA-Shocked mice responding for brain stimulation from the ventral VTA during comparable test intervals. The long-term depressant influence of footshock on self-stimulation from the dorsal VTA was abolished among DALA-treated mice and DALA-associated reductions in self-stimulation from the ventral A10 region among stressed mice were not evident 1 week later. Administration of D-Ala2, N-Me-Phe4, Gly-Ol5-enkephalin (DAGO) (0.01 microg/microl) or D-Pen2, D-Pen5-enkephalin (DPDPE) (1.0 microg/microl) intraventricularly prior to footshock effected an immediate and a delayed antagonism, respectively, of the stressor on self-stimulation from the dorsal VTA, which persisted for 1 week. Prophylactic administration of 0.001 microg/microl DAGO or 0.01 microg/microl DPDPE prior to the stressor failed to influence self-stimulation from the ventral VTA (Experiment 2). Administration of 0.01 microg/microl DAGO or 1.0 microg/microl DPDPE among mice responding for brain stimulation from the dorsal VTA following footshock produced a weak therapeutic effect immediately poststressor, but effected protracted amelioration of footshock-induced reductions of self-stimulation from the dorsal VTA (Experiment 3). Taken together, mu, delta, and mu-delta activation influenced self-stimulation differentially from the dorsal and ventral VTA according to the temporal order of opioid peptide challenge relative to stressor imposition. These data are discussed with respect to stressors, motivational alterations, and the putative modulating influence of endogenous enkephalin activity in subareas of the VTA.

Animals↗

Self-stimulation in the sheep: interactions with ingestive behaviour and light cycle.

Self-stimulation was obtained in 5 adult male sheep using a movable electrode system. The effects on response rate of increases in current, food deprivation and satiation were determined. Interactions between feeding, drinking and self-stimulation over longer periods (5 days) were studied in experiments in which individual sheep lived in an isolated continuously illuminated pen. Experimental conditions were as follows:--(1) Food + water available on operant (FR 30); (2) Operant food and water + self-stimulation; (3) Bowl feeding, ad lib water + self-stimulation; (4) As for condition '3' but with 12:12 light/dark cycle. Finally, sheep were tested for stimulation-bound feeding and drinking. The results obtained in these experiments with the sheep, a ruminant, are compared with those previously found for the pig.

Animals↗

Self-stimulation and alcohol administered orally or intraperitoneally.

The relationships in rats between the reinforcing value of electrical self-stimulation of the brain and varying concentrations of ethanol in the drinking solution (from 5 to 40% v/v alcohol) or in i.p. injections (0.3, 0.6, 1.2, and 1.8 g/kg of alcohol) were studied. The reinforcing value of brain stimulation was quantified using the total time spent in self-stimulation and the number of bar pressings. Results showed that the relationships depended on the ethanol concentration, the degree of reinforcement of the brain stimulation, and the route of administration of the ethanol solution. Particularly, a small dosage injected intraperitoneally or ingested orally accentuated the reward produced by an electrical brain stimulation when the self-stimulation performance was still high. On the contrary, a large dosage of alcohol always dramatically depressed the self-stimulation performance.

Administration, Oral↗

Fos expression following self-stimulation of the medial prefrontal cortex.

Self-stimulation of the medial prefrontal cortex and medial forebrain bundle appears to be mediated by different directly activated fibers. However, reward signals from the medial prefrontal cortex do summate with signals from the medial forebrain bundle, suggesting some overlap in the underlying neural circuitry. We have previously used Fos immunohistochemistry to visualize neurons activated by rewarding stimulation of the medial forebrain bundle. In this study, we assessed Fos immunolabeling after self-stimulation of the medial prefrontal cortex. Among the structures showing a greater density of labeled neurons in the stimulated hemisphere were the prelimbic and cingulate cortex, nucleus accumbens, lateral preoptic area, substantia innominata, lateral hypothalamus, anterior ventral tegmental area, and pontine nuclei. Surprisingly, little or no labeling was seen in the mediodorsal thalamic nucleus or the locus coeruleus. Double immunohistochemistry for tyrosine hydroxylase and Fos showed that within the ventral tegmental area, a substantial proportion of dopaminergic neurons did not express Fos. Despite previous suggestions to the contrary, comparison of the present findings with those of our previous Fos studies reveals a number of structures activated by rewarding stimulation of both the medial prefrontal cortex and the medial forebrain bundle. Some subset of activated cells in the common regions showing Fos-like immunoreactivity may contribute to the rewarding effect produced by stimulating either site.

Animals↗

Optimum parameters for substantia nigra self-stimulation as reflected by peripheral autonomic responses.

Lever-pressing rate, arterial blood pressure, heart rate and respiration were continuously recorded during substantia nigra self-stimulation with systematically varied stimulus parameters in cats. During self-stimulation with fixed pulse train duration, the shorter the pulse train duration the higher was the lever-pressing rate. The rate of responding was a curvilinear function of pulse voltage and frequency during self-stimulation, both at fixed pulse train duration and with self-regulation of pulse train duration. Substantia nigra self-stimulation was always associated with peripheral autonomic changes, which were found within a certain range during self-stimulation with the stimulus parameters producing the highest lever-pressing rate. The preferred level of the peripheral functions under study was characterized by an increase up to 150/130--190/160 mm Hg in blood pressure, an increase up to 190--290/min in heart rate, and an increase up to 60--120/min in respiration. It is concluded that the optimum parameters for substantia nigra self-stimulation may be reflected by the preferred level of peripheral autonomic functions. The results support our earlier suggestion that a peripheral feedback mechanism plays an important role in the timing of lever-pressing behaviour.

Animals↗

Effects of quipazine and of tryptamine on self-stimulation of median raphé nucleus and of lateral hypothalamus in rats.

Separate groups of male Wistar rats were trained to lever press on a continuous reinforcement schedule under which behaviour was maintained by electrical stimulation of the median raphé nucleus (N = 6) or the lateral hypothalamus (N = 6). The effects of several doses of quipazine (2.5-7.1 mg/kg) and of tryptamine (10-80 mg/kg) were assessed with each group. Administration of quipazine resulted in a decrease of median raphé self-stimulation at 5.0 and 7.1 mg/kg. This compound had no statistically significant effect on lateral hypothalamic self-stimulation. Administration of tryptamine resulted in significant decreases in self-stimulation at both sites, however, whereas the effects of this drug were significant at 20, 40 and 80 mg/kg with median raphé self-stimulation, a significant decrease in lateral hypothalamic self-stimulation was only observed at 80 mg/kg. As baseline response rates differed in the two self-stimulation sites, a second group of animals with lateral hypothalamic sites (n = 6) were tested with quipazine (2.5-7.1 mg/kg) at an overall baseline response rate matched to that of the median raphé group. Although a tendency to decrease self-stimulation rates was found in this group, these results were not significant. These data suggest, therefore, that median raphé self-stimulation is more sensitive than lateral hypothalamic self stimulation to disruption by the effects of quipazine and tryptamine.

Animals↗

[Self-stimulation reaction of the hypothalamus in single and repeat administrations of ethaminal sodium].

Pentobarbital facilitated hypothalamic self-stimulation in doses from 1 to 10 mg/kg intraperitoneally. Under concurrent self-stimulation and intravenous self-administration two phases of pentobarbital action were distinctly revealed--activating and inhibitory. The facilitating effect of pentobarbital was blocked by the antiadrenergic drugs, butyroxane, pyrroxane and carbidine as well as was partially antagonized by naloxone. After chronic treatment (20 mg/kg daily) initial inhibition of self-stimulation was replaced by facilitation by days 3-4 of the experiment. Injection of pentobarbital in a daily dose of 3 mg/kg resulted in gradual development of tolerance to the facilitation action of the drug on self-stimulation and in that of dependence. Two types of abstinence reactions after pentobarbital withdrawal are described. The method proposed appears to be sensitive for studying barbiturate dependence.

Animals↗