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PubMedDate not supplied

[Frequency of self stimulation in cats when two parameters are changed simultaneously].

In cats, with electrodes implanted in the lateral hypothalamus a dependence was obtained of self-stimulation frequency (SSF) on paired changes of current strength and each of other stimulation parameters-duration, pulse duration and frequency. In some cases these parameters may independently affect SSF but generally they are in interaction. For stimulation with electrodes located at the level of the hypothalamic ventromedial nucleus, two-peak dependences of SSF on the current strength and the duration of stimulation pulses were obtained. An attempt to describe empirical response surfaces with a regression equation with members of not higher than 4-th order led to an insufficient accuracy of approximation as compared to the results obtained previously on rats. The cause of this insufficiency as well as two-peacked SSF dependencies are discussed in terms of morphofunctional heterogeneity of activated brain structures.

Animals↗
PubMed1986

Changes in response rates and reinforcement thresholds for intracranial self-stimulation during morphine withdrawal.

Rats were implanted with stimulating electrodes in the medial forebrain bundle-lateral hypothalamus and were trained in an auto-titration brain self-stimulation paradigm. When response rates and reinforcement thresholds were stable, the animals were implanted with subcutaneous osmotic minipumps (Alzet, 2ML1) which continually delivered morphine (1.2 mg/kg/hr as the base, n = 16) or saline (10.0 microliter/hr, n = 11). After one week the pumps were removed, and the animals were again tested in the auto-titration paradigm following the daily administration of either saline (spontaneous withdrawal) or 1.0 mg/kg naloxone (precipitated withdrawal). During the eight-day withdrawal phase there was a decrease in the rate of lever-pressing for the morphine dependent animals and this was greatest on the first day. The magnitude of the decrease was greater in the precipitated withdrawal group than in the spontaneous withdrawal group and an increase in the reinforcement threshold occurred only with precipitated withdrawal. Animals in both groups lost weight when measured each morning, but the precipitated group showed greater weight loss during the day. In addition, animals in the precipitated withdrawal group had diarrhea and showed a higher incidence of withdrawal signs than both the non-dependent (control) and spontaneous withdrawal groups. These experiments provide a detailed account of opiate withdrawal following the continuous subcutaneous infusion of a small dose of morphine for one week.

Animals↗
PubMedDate not supplied

Catecholamines and self-stimulation: the action of amantadine and its interaction with amphetamine.

The antiparkinsonian drug amantadine HCl caused a dose-dependent depression of electrical self-stimulation, followed by a dose-dependent enhancement. Neither action was correlated with the differential effects of d- and l-amphetamine at different implantation sites. The initial depression was not prevented by pretreatment with anticholinergic or antiserotonergic agents nor by depression of catecholamine (CA) synthesis. The stimulant effects of amantadine and d-amphetamine summated but did not interact, response rates after d-amphetamine being augmented by pretreatment with amantadine except at intervals at which amantadine was by itself depressant. It is concluded that the initial effect of amantadien is caused by impulse-independent release of a pool of intraneuronal CA, causing dissociation between reinforcement signals and the rat's responses. This is followed by amphetamine-like facilitation of impulse-dependent release; the first action depresses performance, the second enhances it.

Amantadine↗
PubMed1979

Opiate modification of intracranial self-stimulation in the rat.

Studies were conducted to confirm the involvement of central opiate receptors in the expression of opiate modulation of intracranial self-stimulation (ICSS). Biphasic, dose-related changes in ICSS responding are described following IP administration of morphine sulfate (1-25 mg/kg) and levorphanol tartrate (LEV, 0.5-5 mg/kg). Similar patterns of response modification are reported following intraventricular (IVt) administration of LEV (0.01-0.2 muMoles) LEV's enantiomorph, dextrorphan, was not found to elicit comparable effects after either IP or IVt administration. Both the facilitatory and the depressant phases of LEV's action were antagonized by naltrexone (10 microgram, IVt), which had no apparent effect on ICSS by itself. Complete tolerance developed to the suppression of responding by 2.5 mg/kg LEV (IP) but not to the facilitatory effect of 0.5 mg/kg (IP), during a 5-day course of administration. The implications of these results for opiate reinforcement theory are discussed and possible mechanisms are advanced.

Animals↗
PubMed1985

The discriminative stimulus properties and detection thresholds of intracranial self-stimulation: effects of d-amphetamine, morphine, and haloperidol.

A two-choice discrimination task was used to evaluate the effects of psychoactive drugs on the discriminative stimulus properties of brain self-stimulation in rats. In these experiments, brain stimulation served both as a discriminative stimulus and as a reinforcing stimulus, but the two effects were manipulated separately. Animals were trained to a criterion of 95% correct in choosing between two levers, and when this level of accuracy was reached, the ability to choose correctly remained stable over an 8-month period. Increasing the current strength of the discriminative stimulus from zero to 100% of the training current produced a graded increase in the number of trials completed on the appropriate lever. The discriminative effects produced by brain stimulation were evaluated pharmacologically by using three prototypical psychoactive drugs in an attempt to change the detection threshold for the discriminative stimulus. Morphine, d-amphetamine, and haloperidol, drugs that reliably alter reinforcement thresholds for brain stimulation, failed to change detection thresholds. These results demonstrated that: brain stimulation produces potent and reliable discriminative effects and the effects of psychoactive drugs on detection thresholds can be dissociated from their effects on reinforcement thresholds for brain stimulation.

Animals↗
PubMed1986

Neurotransmitters, pathways and circuits as the neural substrates of self-stimulation of the prefrontal cortex: facts and speculations.

Through a multidisciplinary approach considerable progress has been made in understanding the neural substrates of self-stimulation (SS) of the medial prefrontal cortex (MPC). Thus, neuroanatomical studies have revealed that intrinsic neurones in the MPC seem to be the central elements responsible for initiating and maintaining this phenomenon in this area of the brain. Complementary to this central finding are the electrophysiological and neurohistological data reviewed here, showing that neurones in the MPC are directly activated and have monosynaptic feed-back connections with neurones located in areas which also support SS. These findings have given rise to the hypothesis that several single feed-back pathways or single circuits exist between points of SS in the MPC and points of SS in other areas of the brain. This hypothesis implies that SS in a particular area would depend not only on the intrinsic local activity induced by the electrical stimulation but on the functional and specific activity of other nuclei in the brain. The fact that lesions of single circuits, which are apparently involved in SS of the MPC such as the medial prefrontal cortex-ventrotegmental area-medial prefrontal cortex and medial prefrontal cortex-n. dorsomedialis of the thalamus-medial prefrontal cortex, do not produce a permanent decrease of SS, together with the finding that transynaptic connections seem to exist between MPC and other areas of the brain, suggests further that a complex rather than several single independent circuits could be at the neural basis of SS of the MPC. If that were the case, then SS of the MPC would not only depend upon local and single feed-back activity but upon specific functional feed-back activity among the nuclei, which in turn have single feed-back connections with the MPC (see the concept of 'complex circuit' outlined in the section of Behavioural studies). On the basis of this hypothesis no permanent changes should be expected after lesions of single pathways since physiological and even anatomical compensation could be reached through the rest of the undamaged circuit. That terminals containing specific neurotransmitters exist in layers of the PC where electrodes for SS are located has been reviewed in this paper. Some of these neurotransmitters have been suggested to be part of the local substrates activated by SS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Scopolamine increases nonreinforced behavior in an intracranial self-stimulation discrimination paradigm.

The effects of several doses of systemic scopolamine administration on brain-stimulation reward from the A10 nucleus of the ventral tegmental area (VTA) were evaluated. The intracranial self-stimulation (ICSS) task involved a two-hole nose-poke procedure allowing for the assessment of both reinforced (correct) and nonreinforced (incorrect) performance levels as a function of varying current intensities. Scopolamine (0.75, 1.5, and 3.0 mg/kg) was found not to alter the rate-intensity functions derived from descending and ascending presentation of seven current levels. However, when nonreinforced behavior was considered significant increases in error responding were evident following scopolamine injection. These results are consistent with the known disinhibitory and perseverative properties of scopolamine, and indicate that the previously reported positive actions of peripheral administration of anticholinergic drugs on ICSS likely involved a drug-induced rate-enhancement of reward-unrelated performance variables.

Animals↗
PubMed1986

Temporal characteristics of electrical self-stimulation reward: fatigue rather than adaptation.

Using a Y-maze preference test paradigm, we examined the temporal characteristics of the neural network subserving self-stimulation reward. Rats were given a choice between two pulse trains of stimulation, which varied in duration and pulse frequency. The results showed that increasing the pulse frequency decreases the duration at which the rewarding effectiveness of brain stimulation reaches an asymptote. The data also indicated that when prolonged stimulation is delivered at a high pulse frequency, the initial pulses contribute the most to the rewarding effect. Later pulses are affected by the reduced ability of the neurons or synapses to transmit signals along the neural network due to fatigue. The data are explained in terms of an improved model of summation involving more than one integrator and fatigue.

Adaptation, Physiological↗
PubMed1984

Comparative effects of beta 2-adrenoceptor agonists on intracranial self-stimulation, Sidman avoidance, and motor activity in rats.

The effects of beta-adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on lever-pressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS lever-pressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although beta-adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance.

Adrenergic beta-Agonists↗
PubMed1983

Central catecholamine metabolism and hypothalamic self-stimulation behaviour in two inbred strains of mice.

These experiments were conducted in order to better understand the role of catecholaminergic neurons in intracranial self-stimulation behaviour (ICSS) elicited from the lateral hypothalamus (LH). Two strains of mice which differ in their ICSS rate and their thresholds were studied. In a first time, we compared the catecholamine (CA) content and activity in various parts of the brain including cell bodies and nerve terminals of the man CA bundle. We used for this determination a high performance liquid chromatographic separation and an electrochemical detection. We observed that the BALB/c strain is distinguished by a higher CA activity than the DBA/2 strain. This correlates with a higher ICSS response rate in the BALB/c strain. The effects of stimulation on CA metabolism were then investigated, the electrodes being implanted specifically either in the dorsal or the ventral part of the LH and the biochemical data obtained analysed separately. Significant enhances of CA turn-over (TO) were noted in nerve terminals as hippocampus, cortex and accumbens. These results provide further evidence for the involvement of dorsal noradrenergic bundle and mesolimbic dopaminergic bundle in LH ICSS. Stimulation in the dorsal part of the LH produced the higher ICSS rate and seemed to induce a large variation of the CA TO. We noted also that the CA metabolism was always more altered in the DBA/2 than in the BALB/c strain, which is surprising in regard to the behaviour and remains unclearly explained.

Animals↗
PubMed2000

Intracranial self-stimulation and sucrose intake differ as hedonic measures following chronic mild stress: interstrain and interindividual differences.

The present study was designed to assess the utility of sucrose intake and intracranial self-stimulation (ICSS) as hedonic measures for chronic mild stress (CMS) induced behavioural deficits. Wistar and PVG hooded rats were exposed to a variety of mild stressors, e.g. periods of food and/or water deprivation, soiled cage, light/dark reversal, confinement to small cages and pairing, during 6-9 weeks. The intake of 1% sucrose solution was significantly reduced in stressed PVG hooded rats compared to control animals. The sucrose intake in stressed Wistar rats remained unaltered, indicating that CMS-induced decreases in sucrose intake are strain dependent. However, sucrose intake has in our experience been shown to be unreliable as the observed decreases following CMS were inconsistent over time. ICSS behaviour was evaluated from rate/frequency functions by determining the frequency that supported 50% of maximal response rate. Neither the Wistar nor the PVG hooded rats showed an overall decrease in ICSS behaviour following CMS. However, the ICSS measures revealed interindividual differences in both rat strains. In the stress groups a subgroup (14 +/- 2.4%) of rats progressively exhibited an attenuated ICSS behaviour. These findings may reflect the interindividual variability observed in humans as stress does not invariably lead to depression. The model may in its present form be used to study the pathophysiology of depressive disorders. However, the utility of the CMS model to study antidepressant drug actions has to be questioned. Our results show there is a need for rat strains in which there is a greater sensitivity for detecting stress effects. It emphasises the fact that replication of CMS-induced decreases in ICSS behaviour can be as problematic as inducing decreases in sucrose intake.

Animals↗
PubMed1976

Brain stem self-stimulation attenuated by lesions of medial forebrain bundle but not by lesions of locus coeruleus or the caudal ventral norepinephrine bundle.

Midbrain tegmental intracranial self-stimulation (ICSS) was not attenuated by ipsilateral or bilateral locus coeruleus lesions. Certain of these lesions were followed by histochemical confirmation that the majority of locus coeruleus neurons was destroyed, and biochemical evidence that over 80% of the cortical norepinephrine was depleted. To test the possibility that the surviving ICSS was due to stimulation of another norepinephrine system, histochemically verified ipsilateral or bilateral lesions of the ventral norepinephrine bundle were administered to a second group of midbrain tegmental ICSS animals. These lesions resulted in marked loss of body weight, but had no effect on ICSS. In a third experiment, lesions were made in the medial forebrain bundle (MFB) ipsilateral to midbrain tegmental ICSS electrodes. These lesions resulted in attenuation of ICSS which was directly proportional to the extent of MFB damage. On the basis of these data alone, however, it was not possible to identify the ciritical fibers supporting ICSS. It was oncluded that the locus coeruleus does not play a necessary role in midbrain tegmental ICSS.

Animals↗
PubMed1995

The effects of ventral tegmental administration of GABAA, GABAB and NMDA receptor agonists on medial forebrain bundle self-stimulation.

Using a conditioned discrimination ICSS paradigm, rate-current intensity functions were determined for both reward- and nonreward-associated responding for electrical self-stimulation of the MFB following intra-VTA infusion of baclofen, muscimol and N-methyl-D,L-aspartate (NMDLA). A low dose (0.064 microgram/0.5 microliter) of the GABAB receptor agonist, baclofen, microinjected into the VTA, ipsilateral to the lateral hypothalamic stimulating electrode, resulted in a rightward shift of the ICSS curve without significantly influencing either maximal rates of operant responding for electrical brain stimulation or nonreinforced performance levels. Increases in MFB current thresholds were also evident after infusion of higher doses of baclofen (0.128, 0.26 and 0.52 microgram) into the ventral tegmentum. Intra-VTA administration of the GABAA receptor agonist, muscimol (0.006, 0.012, 0.025 and 0.05 microgram) and NMDA receptor activation by NMDLA (0.5, 1, 2 and 5 micrograms) did not affect reward thresholds; however, the low dose of muscimol and the high dose of NMDLA elicited behavioral activation resulting in reward-unrelated performance effects. These results implicate the specific involvement of the GABAB receptor in the reward neurocircuitry of the VTA.

Animals↗
PubMedDate not supplied

[Behavioral, electrophysiologic and vegetative correlates of self stimulation in dogs].

Summary electrical activity of different brain structures (chiefly the hippocampal theta-rhythm) and cardiac and respiratory rhythms were recorded during self-stimulation (SS) in dogs. Emotional-motivational excitation in dogs, preceding SS, is attended with a moderate increase in theta-activity in the hippocampus. The SS period is characterized by desynchronization of the electrical activity, the appearance of high-frequency rhythmics and diminished theta-rhythm. After withdrawal of the pedal, hypersynchronization of the theta-rhythm sets in in most of the structures studied. SS is accompanied by considerable shifts of the cardiac and respiratory rhythms. The dynamics of behavioral, electrophysiological and vegetative shifts during SS in dogs points to a successive involvment of the brain mechanisms of search, positive reinforcement and emotional-negative interruption of the pedal pressing series. Complex interaction of the three mechanisms underlies the external phenomenology of the SS instrumental conditioned reflex.

Amygdala↗
PubMed1991

Improvement of shuttle-box avoidance with post-training intracranial self-stimulation, in rats: a parametric study.

Rats were trained in a two-way active avoidance task followed immediately by a lateral hypothalamic intracranial self-stimulation (ICSS) treatment, during 5 consecutive days. The effects of the number of ICSS trains allowed (0, 500, 2500 or 4500) were studied upon acquisition and long-term retention (LTR, 10 and 30 days). The number of ICSS trains administered and the number of avoidances at the last acquisition session (5th) showed a positive lineal relation, that is, the more number of ICSS trains, the more number of avoidances. The level of learning achieved during the 5th session was maintained after the LTR periods in all experimental groups. It is concluded that the number of ICSS trains could be a critical parameter in the facilitatory effect of lateral hypothalamic ICSS upon learning, and it is suggested that the facilitatory effect of post-training lateral hypothalamic ICSS might be due to the activation of general activatory neural systems.

Animals↗
PubMed1986

Lesions of connections of the medial prefrontal cortex in rats: differential effects on self-stimulation and spontaneous motor activity.

The effects of lesions of the mediodorsal nucleus of the thalamus (MD) and the nucleus caudate putamen (CP) on self-stimulation (SS) of the medial prefrontal cortex (MPC) were investigated. After bilateral electrolytic lesions of the MD or the anteromedial segment of the CP, SS rate and spontaneous motor activity (SMA) were measured. Both MD and CP lesions induced a significant decrease in SS. After 8 days post-lesion, SS rate recovered to pre-lesion levels. SMA did not change significantly after MD lesion. However, SMA showed a significant decrease the 1st and the 5th days after lesioning the CP. The results suggest that the MD and possibly the CP are associated with SS, although it appears that they do not have an essential but rather a modulatory role. The recovery of SS occurs within a few days, presumably due to the compensatory effect of other pathways and structures. The results are also discussed in relation to the effect found after electrolytic lesion of ventrotegmental area and locus coeruleus.

Animals↗
PubMed2002

Intracranial self-stimulation facilitates memory consolidation, but not retrieval: its effects are more effective than increased training.

To evaluate possible differential effects of lateral hypothalamic intracranial self-stimulation (ICSS) on memory consolidation and retrieval, independent groups of Wistar rats were trained in a single session of two-way active avoidance task (acquisition session) and tested 24 h later (retention session). The post-ICSS groups received an ICSS treatment immediately after the acquisition session, and the pre-ICSS groups received the same treatment immediately before the retention session. Because the ICSS effects on memory seem to be dependent on the initial performance level shown by the subjects, the possible influence of initial training (number of trials) on ICSS effects was also studied. Therefore, we used different control and experimental groups, which received either 30 or 50 trials in the acquisition session. Post-training ICSS facilitated the 24-h retention in both training conditions (30 and 50 trials). In contrast, pre-retention ICSS treatment did not facilitate performance in the retention test. We also observed that post-training ICSS was more effective for improving the 24-h retention than increasing the initial training from 30 to 50 trials. This findings confirm that ICSS treatment improves memory consolidation and suggest that it might not affect memory retrieval mechanisms.

Animals↗