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[Ultrastructural changes in the septum pellucidum of the cat brain after its long-term self-stimulation].

During prolonged electrical stimulation of the septum (self-stimulation 2-3 h daily for 2.5 months) perikarion of most neurons, situated around the tip of the stimulating electrode undergoes peripheral chromatolysis, less part of the neurons is shrunk, mitochondria are desorganized, invaginations of the nuclear membrane occur more often and deeper. Intercellular clefts are sharply dilated, profiles of altered myelin fibers are observed, presynaptic terminals decrease in their number. Axonal terminals with agglutinated vesicles become more numerous. In other terminals osmiophilic bodies and membranous inclusions are revealed. Under electric stimulation a sharp reaction of glial cells, especially astrocytes is observed. One group of astrocytes participate in phagocytosis of the degenerating structures, while the other--in formation of the glial scar.

Animals↗

Comparison of the effects of D-amphetamine on FI and DRL schedule performance of self-stimulating rats.

Six rats bar-pressed for intracranial self-stimulation in a Skinner box on fixed interval and differential reinforcement of low rate schedules with an interval parameter of 1.3 s. After amphetamine timing efficiency was reduced immediately on both the schedules; it recovered after 60 min on the DRL schedule but not within 120 min on the FI schedule. Response rates increased on both the schedules. The increased response rates correlated with the low efficiency on the DRL but not on the FI schedule. The selective sparing of DRL performance is in line with the similarity between the effects of amphetamine and frontal cortical lesions.

Animals↗

Self-stimulation from the mesencephalon following intraventricular interleukin-2 administration.

Intracranial self-stimulation was evaluated among CD-1 mice responding for brain stimulation from the dorsal and ventral aspects of the ventral tegmental area (VTA). Intraventricular interleukin-2 (IL-2) administration (5 ng) in a 1-microl volume elevated the stimulation frequency required to effect half-maximal responding for brain stimulation from the dorsal A10 region 15 min, 24 h, 48 h, and 1 week following drug administration relative to vehicle-treated animals. Intraventricular IL-2 administration did not influence responding for brain stimulation from the ventral A10 area, and performance of these animals was indistinguishable from the performance of vehicle-challenged animals implanted with a stimulating electrode in the ventral A10 area. These data suggest that central IL-2 administration reduces the value of previously rewarding brain stimulation from subregions of the VTA. The implications of these data for behavioural pathology are discussed.

Animals↗

Effects of illumination level on the rat's rhythmicity of brain self-stimulation behavior.

Rhythmic patterns in the rat's brain self-stimulation behavior were analyzed across levels of illumination, including conditions of constant illumination (LL), constant darkness (DD), and light-dark cycles (LD 12:12). LD entrainment was achieved with light intensities ranging from 0.25 to 440 lux, and little or no change was found in the phase-angle difference between the dominant spectral peak and the light transitions. Under constant conditions, the circadian period (tau) increased in proportion to illumination level, with means ranging from 24.10 h (DD) to 25.90 h (LL 440 lux). tau increased linearly as a function of long I within the range of 0.25 to 30 lux, yielding a change of 0.28 h for a 10-fold increment in illumination level, a value which closely matches Aschoff's [3] preliminary estimate of delta tau/delta ILL for the rat. The circadian spectral component was influenced by several factors. (1) Re-entrainment protocol. Given a succession of LL conditions without entrainment segments in between, circadian rhythmicity was obscured at high illumination levels. (2) Duration of LL exposure. Even following an entrainment segment, long-term LL resulted in reduced power or loss of the circadian component. (3) LD vs LL. Spectral power was consistently higher under entrainment than under corresponding LL intensities, and there was a trend toward reduced power as a function of LL intensity. A wide range of ultradian spectral components was found across conditions. Under entrainment, most such components were harmonics of the circadian fundamental; under constant conditions, the frequency relationships were relatively variable.

Animals↗

Self-stimulation and amphetamine: tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate.

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.

Amphetamine↗

Facilitation of self-stimulation behavior following intracerebral microinjections of opioids into the ventral tegmental area.

The intracerebral microinjection technique was used to localize sites in the brain where morphine facilitated the self-stimulation rate at hypothalamic electrode sites. Bilateral injections of morphine (2 x 1 microgram) into the ventral tegmental area and substantia nigra produced the strongest enhancement at the shortest latencies. At these sites, bilateral injections of 200 ng of morphine also produced a significant enhancement whereas a dose of 50 ng was below threshold for the rate increasing effect. The enhancement by morphine was effectively antagonized by naloxone (5 mg/kg). When injected bilaterally into the same area, D-Ala2-Met5-enkephalinamide (2 x 1 microgram) also induced a strong enhancement of self-stimulation lasting for 70 minutes. A possible dopaminergic substrate for the opiate induced behavioral stimulation is discussed.

Animals↗

Diode-pumped passively Q-switched picosecond Nd:GDxY1-xVO4 self-stimulated raman laser.

An efficiency of 8.2% is demonstrated for a diode-pumped passively Q-switched self-stimulated Raman laser with an a-cut mixed vanadate crystal, Nd:Gd0.8Y0.2VO4. At 2.2 W of incident pump power, the self-stimulated Raman laser produces pulses as short as 660 ps at a Stokes wavelength of 1175 nm with 2.7 microJ of energy per pulse at a 66-kHz repetition rate.

Journal Article↗

Differential effects of opioid peptides administered intracerebrally in loci of self-stimulation reward of lateral hypothalamus and ventral tegmental area--substantia nigra.

Leu-enkephalin, leu-enkephalinamide, ala-leu-enkephalin, met-enkephalin and dynorphin-A[1-13] were administered in microinjection into one of the self-stimulation sites of SN-VTA or MFB-LH and the electrical self-stimulation (SS) of the injected site and of the second site was recorded. The study revealed that the leu-enkephalin and the leu-enkephalinamide inhibited the SS of SN-VTA and produced no effect on the SS of MFB-LH, when administered into these sites. The MFB-LH injection, however, facilitated the SS of SN-VTA. The effect of ala-leu-enkephalin injection in MFB-LH was similar to the above, but the effect of the injection in SN-VTA was different in that it caused the facilitation of its SS and not the depression as seen with leu-enkephalin. Met-enkephalin injections in the two regions caused no direct or indirect changes of the SS of the regions. Dynorphin injection in SN-VTA facilitated its SS, like the injection of ala-leu-enk, but dynorphin injections in MFB-LH produced no effects. The results essentially demonstrate the differences in the effects of the different opioids in the reward system of the SN-VTA, and it is discussed that these differences are probably due to the preferences in the types of the receptors upon which these opioids act in the SN-VTA neuronal organisation. The results also demonstrate the major difference in the organisation of the reward substrate of the MFB-LH from that of the SN-VTA, as the effects of the opioids in the MFB-LH are markedly different or none compared to the effects in the SN-VTA.

Animals↗

The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum.

The present experiments were designed to test further the idea that 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative dopamine (DA) D3 agonist, has effects at DA autoreceptors to reduce intracranial DA levels and to reduce behaviours that are DA-dependent. Rats were trained to respond on a self-stimulation protocol for electrical stimulation to the ventral tegmental area (VTA). Each press of a lever delivered a 0.5 s train of square wave, 1.5 ms duration, 100 Hz, 90-120 mA stimulation. Systemic administration of 7-OH-DPAT at 0.01-0.3 mg/kg i.p., quickly dose-dependently reduced responding. Electrical stimulation using similar parameters to those that supported self-stimulation were then applied to the VTA of anaesthetized rats. Fast cyclic voltammetry (FCV) revealed that this stimulation released DA in the nucleus accumbens (NAC). 7-OH-DPAT i.p. (0.1-3.0 mg/kg) quickly and potently reduced the size of the DA-generated voltammetric signal. This effect of 0.3 mg/kg 7-OH-DPAT was not blocked by sulpiride (60 mg/kg, i.p.) a D2-specific antagonist that may preferentially block D2 autoreceptors. These data are discussed with reference to the possibility that 7-OH-DPAT reduces the release of dopamine in the NAC, at D3, but not at D2, autoreceptors and that this in turn may reduce the rewarding effect of VTA stimulation.

Animals↗

Effect of glucoprivation on self-stimulation rate-frequency functions.

In a series of two experiments using rats, the effect of glucoprivation, induced by 2-deoxy-D-glucose (2-DG) or insulin injections, on self-stimulation rate-frequency functions, was evaluated at two levels of current intensity. At the higher current intensity, neither insulin nor 2-DG produced a significant change in rate-frequency function parameters. At the lower current intensity, insulin suppressed asymptotic responding while 2-DG produced a lateral curve shift. Results of this study would argue that glucoprivation produces changes in self-stimulation at lateral hypothalamic electrodes that are: a) unrelated to the involvement of the neurons in stimulation-induced eating, b) are most notable when a smaller number of reward relevant neurons is stimulated, and c) can be differentially attributed to changes in motoric performance capacity during insulin tests and to changes in the reward value of stimulating current during 2-DG tests.

Animals↗

The role of corticocortical projections in self-stimulation of the prelimbic and sulcal prefrontal cortex in rats.

Four experiments were performed to assess the nature of the contribution of the corticocortical projections between the prelimbic and sulcal divisions of the rat prefrontal cortex to self-stimulation (SS) of these sites. The first experiment showed that transection of these projections by parasagittal knife cuts or bilateral electrolytic lesions of the prelimbic cortex had no effect on SS of the sulcal cortex. The second experiment demonstrated that SS of the prelimbic cortex could be obtained after transection of the corticocortical projection path. The third experiment demonstrated that the deficit in prelimbic SS, seen to follow such bilateral transections, is a function of the amount of exposure to the stimulation given to the animals after the lesion. The fourth experiment showed that the stimulation-dependent process underlying the acquisition of prelimbic and sulcal SS could be dissociated by the knife cuts. The discussion focused on the implications of these findings for an account of prefrontal self-stimulation behavior.

Animals↗

An analysis of dorsal and median raphe self-stimulation: effects of parachlorophenylalanine.

The role of serotonergic systems in intracranial self-stimulation (ICSS) of the dorsal and median raphe nuclei of rats was investigated. Intragastric administration of 400 mg/kg of parachlorophenylalanine (PCPA) depressed ICSS rates in the group with dorsal raphe electrode placements over a similar time course to the depletion of brain serotonin which results from treatment with PCPA. An intrasessional analysis of these behavioral changes on the fourth day after PCPA revealed that dorsal raphe ICSS was depressed over both halves of the 2 hr test session, whereas a significant depression in median raphe ICSS occurred only in the last hr of the session. The data from these studies suggest that brain serotonin systems contribute to the phenomenon of brain-stimulation reward in the dorsal and median raphe nuclei. The involvement of multiple neurochemical substrates of brain stimulation reward is discussed.

Animals↗

[Pharmacological analysis of the serotonin- and glutamatergic mechanisms in the suppressive effect of neuroleptics on the pedal self-stimulation of the ventral tectum of the midbrain].

The serotoninergic mechanisms of neostriatum were found to be involved into the suppressive effects of droperidol, fluphenazine, haloperidol, thioridazine but not those of trifluoperazine, clozapine and aminazine on the midbrain ventral tegmentum self-stimulation. The glutamatergic mechanisms of neostriatum and nucleus accumbens septi play a minor role in attenuation of tegmental self-stimulation with droperidol, fluphenazine, trifluoperazine and clozapine but these mechanisms seem to be responsible for the suppression of "reward" phenomenon with haloperidol, thioridazine and aminazine.

Animals↗

Long term results of periventricular gray self-stimulation.

Thirty patients were operated upon, with chronic implantation of self-stimulating devices for stimulation of the posterior periventricular gray matter for pain control. Three patients required removal of the electrodes because of failure of adequate pain control during the period of percutaneous testing, and five patients report on long term follow-up that they have had no pain relief with stimulation, and have discontinued it. Four patients describe minor relief of pain, and 18 patients report significant relief of pain with stimulation. Therefore, 18 patients, or 66% of the 27 patients having implantation, are considered to have had successful operations, and 12 of the patients are considered failures. Stimulation for brief periods of time, such as 5 to 30 minutes every 2 to 12 hours has been found adequate for control of chronic pain with minimal side effects and a low complication rate.

Analgesia↗

Detailed analysis of estrous-related changes in wheel running and self-stimulation.

Previous studies have demonstrated that a number of behaviors change their probability of occurrence during the estrous cycle. Wheel running is known to show estrous-related changes while reports upon intracranial reinforcement (self-stimulation, ICS) have been equivocal. The present studies examined both behaviors to further resolve the underlying behavioral determinants of these estrous effects. Data for wheel running and intracranial self-stimulation behaviors of adult female Holtzman rats were collected nightly on a minute by minute basis across the estrous cycle. It was found that: (a) both behaviors showed significant estrous-related changes in frequency; (b) the two behaviors occurred in discontinuous episodes (bursts) during the dark phase of the diurnal cycle; and (c) of three burst parameters (number/session, average length, rate of response), number proved the best predictor of estrous-related behavioral change. Burst number may reflect an important motivational parameter underlying estrous-related changes in behavior.

Animals↗

Effect of beta-phenylethylamine and d-amphetamine on electrical self-stimulation of brain.

beta-phenylethylamine (PEA) has been viewed as amphetamine-like in its effects on behavior. Support for this putative similarity of action has been derived primarily from observations that both of these structually related compounds increase locomotor activity in a dose-related manner and at higher doses evoke stereotypies. Since d-amphetamine (d-A) produces a dose-related increase in the rate of bar pressing for electrical stimulation of the medial forebrain bundle, the effect of PEA on this behavioral paradigm was examined. Male Long-Evans rats implanted with bipolar electrodes self-administered 250 msec 60 Hz constant current sine wave trains over a 30-70 micronA range of intensities in daily 20-min tests. Over a range of 1-40 mg/kg IP of PEA, a dose-related decrease in self-stimulation rate was observed; pretreatment with para-chlorophenylalanine or alpha-methyl-para-tyrosine did not alter the response to 2.5 or 3o mg/kg IP of PEA. Since within the dose range of PEA used in this study a dose-related increase in locomotor activity was observed, and since d-A increases self-stimulation rate at doses that increase locomotor activity, it would seem that there are qualitative differences in the actions of d-A and PEA on behavior.

Animals↗

[Self-stimulation of supracallosal bundle (SCB) and associated behavior comparing to those of prefrontal cortex (PFC) (author's transl)].

The supracallosal bundle (SCB) and prefrontal cortex (PFC) receive projection from medial forbrain bundle (MFB) of the lateral hypothalamus (LH) in relation to reward system. The major purpose of the present study was to compare the intracranial self-stimulation (ICSS) rate of both the SCB and PFC with special emphasis on its associated behavior. The results obtained were as follows: 1) self-stimulation was obtained with electrodes historogically varified as being in the SCB (16 of 23 electrodes positive for ICSS) and the medial PFC (3 of 16 electrodes positive for ICSS). Electrodes dorsal and far lateral to the SCB and PFC were mainly negative (see Fig. 1). 2) Rats with SCB or PFC electrodes, chiefly showed a rearing associated with its ICSS. When stimulation electrodes were more posterior or lateral sites in the SCB and PFC, clonic movements of forelimb and head were occasionally observed (Fig. 1). 3) For neuron in the LH, stimulation of the SCB via chronic electrodes positive for ICSS produced two characteristic types, i.e. postinhibitory rebound type (Fig. 2A) and driven inhibitory type (Fig. 2B-1). It was suggested that fibers of MFB were activated by stimulating SCB-ICSS sites.

Animals↗