Ventral Tegmental Self-stimulation Research Articles

GABAergic inactivation of basolateral amygdala alters behavioral processes other than primary reward of ventral tegmental self-stimulation

Although recent work on amygdalar function has concentrated on a role in fear and anxiety, a possible role in reward processes continues to be considered. This function may occur via anatomical connections between the basolateral amygdala (BLA) and the mesoaccumbens dopamine (DA) system (i.e., ventral tegmental area [VTA] to nucleus accumbens septi [NAS]), particularly at the level of the NAS. The current experiments investigated a possible role of the BLA in the reward of intracranial self-stimulation (ICSS) of the VTA. Rats were trained in either an autotitration ICSS task or a rate-frequency ICSS task. We examined the effect of intra-BLA injections of muscimol, a GABA A agonist which inhibits the firing of most neurons, on VTA ICSS in both behavioral procedures. The injections produced a pattern of behavioral change which, across the two tasks, was more consistent with a change in behavioral processes other than primary reward. Possible processes include cost/benefit analysis and incentive motivation.

Validation of stress-induced anhedonia and ventral tegmental self-stimulation behavior in the rat

Validation of stress-induced anhedonia and ventral tegmental self-stimulation behavior in the rat

Differential effects of ondansetron, haloperidol and clozapine on electrical self-stimulation of the ventral tegmental area

The effects of 5-HT(3), receptor blockade with ondansetron (0.025-0.2mg/kg) on intracranial self-stimulation of the ventral tegmental area were compared with effects of the typical antipsychotic drug haloperidol (0.01-0.3mg/kg) and the atypical antipsychotic drug clozapine (1.25-10mg/kg). Rats were trained to self-stimulate using unipolar ventral tegmental electrodes (200µm diameter) to deliver 1s trains of 0.2ms cathodal pulses of constant current stimulation as a reinforcer. The animals were tested daily in frequency threshold tests. The frequency that maintained half maximal response rates (M50) and the maximal number of responses at a single frequency (RMAX) and the number of responses per session (TRESP) were used to measure drug effects. Ondansetron had no effects on the behavioural measures in this study. Haloperidol induced a significant increase in M50 at 0.3mg/kg without altering RMAX; TRESP was reduced by 0.1 and 0.3mg/kg of this drug. Clozapine increased M50 at 5.0mg/kg; following 10.0mg/kg of clozapine responding was completely abolished and no M50 measure could be calculated. Clozapine reduced RMAX at 1.25, 5.0 and 10.0mg/kg; TRESP was decreased by 5.0 and 10.0mg/kg of clozapine. The present results indicate that ondansetron had no measurable effects under conditions in which haloperidol and clozapine increase reinforcement thresholds and decrease response rates maintained by ventral tegmental self-stimulation.

Effects of continuous naloxone administration on ventral tegmental self-stimulation

Continuous subcutaneous administration of naloxone (3 mg/kg/h), shifted ventral tegmental self-stimulation rate-frequency curves to the right, without suppressing behavioral performance. In addition this chronic blockade of opioid receptors altered μ binding parameters in the hippocampus and olfactory tubercle of naloxone-treated animals. These findings speak to the role opioid peptides play in the mediation of brain stimulation reward.

Effects of naltrexone on nucleus accumbens, lateral hypothalamic and ventral tegmental self-stimulation rate—frequency functions

Rats trained to lever-press for electrical stimulation of the nucleus accumbens, lateral hypothalamus, or ventral tegmental area, were tested with a range of stimulation frequencies to assess the effects of naltrexone (2.5, 5.0, 10.0, 20.0 mg/kg, i.p.) during sessions beginning 15 or 45 min after injection. Naltrexone, when effective, shifted the rate-frequency functions to the right; the magnitude of the effect depended on site of stimulation and on the delay after injection. The greatest effect was observed with stimulation of the nucleus accumbens and the least with stimulation of the ventral tegmental area. There was a greater attenuation of responding during the late test sessions than during the early ones. The time course of naltrexone's effect on brain stimulation reward was determined for the highest dose by measuring a rat's rate of responding over a 3 h period in sessions with immediate access (5-min delay) or delayed access (45-min delay) to stimulation. The greatest decreases in responding were observed 45, 65, and 85 min after injection and the delay in access made little difference. The fact that the drug was more effective 45 min after injection explains some of the inconsistencies in the literature; the fact that its effectiveness was independent of early exposure to stimulation would suggest pharmacological rather than experiential factors as the explanation of the delayed effectiveness.

Catecholamines and endogeneous opioids in ventral tegmental self-stimulation reward

Midbrain dopaminergic pathways and opioid receptor systems have been implicated in the reward experienced in electrical intracranial self-stimulation behavior. In the present experiment, the influence of graded doses of the dopamine antagonist haloperidol and of the agonist cocaine were investigated on electrical self-stimulation reward, elicited by electrodes located in the ventral tegmental area. A threshold method, which is rather insensitive for aspecific motor effects, was applied to determine the reward of self-stimulation. The method allowed to determine simultaneously the rate of lever pressing for self-stimulation. All doses of haloperidol and cocaine were administered with and without the opioid antagonist naloxone, in order to investigate the interaction between dopaminergic and opioid modulation of reward. Haloperidol lowered and cocaine tended to increase the response rate, whereas cocaine but also haloperidol lowered the self-stimulation threshold. The effects appear to be dose-dependent. Naloxone did not interact with the effect of the drugs on threshold and it lowered the response rate, but in the haloperidol-treated rats only. It is concluded that dopamine is involved in the reward of electrical self-stimulation elicited from the ventral tegmental areaand that this involvement is independent of endorphin systems, suggesting the existence of separate catecholamine and opioid mechanisms modulating brain reward.

Refractoriness of neurons mediating intracranial self-stimulation in the anterior basal forebrain

The post-stimulation excitability of neurons mediating electrical self-stimulation of the anterior basal forebrain was evaluated psychophysically in the rat. Rats with electrodes in the nucleus accumbens, caudate nucleus, lateral preoptic area, diagonal band, or anterior medial forebrain bundle pressed a lever to earn 0.5-s trains of conditioning (C) and test (T) pulse pairs. The C-T interval was systematically varied and the effectiveness of the T-pulse was estimated by measuring the frequency of pulse pairs required to sustain criterion responding. All sites tested demonstrated similar recovery; T-pulse effectiveness, normalized against the effect of the C-pulse, was lowest at delays of 0.4–0.8 ms and it rose monotonically until 5 ms when it achieved an effectiveness plateau of one. Increasing the current of the T-pulse by 50 or 60% failed to hasten recovery, suggesting that the recovery profiles primarily reflect the activation of neurons very soon after emergence from absolute refractoriness. Compared to lateral hypothalamic and ventral tegmental self-stimulation, the neurons that support self-stimulation in the ventral basal forebrain recover more slowly; recovery here is only about half done by the time lateral hypothalamic placements demonstrate complete recovery.

Long-term desipramine treatment attenuates clonidine-induced suppression of ventral tegmental self-stimulation

Long-term administration of the tricyclic antidepressant desipramine did not change the rate of self-stimulation responding in the A10 (ventral tegmental) area but significantly attenuated the suppressive effect of the selective α 2-adrenergic agonist clonidine on this behavior. These findings demonstrate an involvement of noradrenergic mechanisms in the regulation of ventral tegmental self-stimulation and further suggest that adaptive changes in inhibitory presynaptic noradrenergic receptors may be involved in desipramine's antidepressant effects.

Ventral tegmental self-stimulation, sensory reactivity and pain reduction in rats selected for high and low rates of lateral hypothalamic self-stimulation

Ventral tegmental self-stimulation (VTSS) was studied in 56 male rats of four genetic lines (LC1-Lo, LC1-Hi, LC2-Lo, LC2-Hi), which differed in their inherent tendencies to self-stimulate the lateral hypothalamus. It was found that LC2-Hi rats engage more in VTSS than do rats of the LC2-Lo line. No differences were observed between the LC1-Hi and -Lo lines. In a second experiment, the LC2-Hi and -Lo lines were compared as to peripheral pain thresholds (36 animals) and VT-induced-analgesia (21 animals). Genetically low self-stimulators of the LC2 selection program were found to be more sensitive to acute peripheral pain and to VT analgesic influences than are their high counterparts. Theoretical implications are discussed.

Ventral tegmental analgesia in two strains of rats: Effects of amphetamine, naloxone and parachlorophenylalanine

Pain sensitivity and analgesia induced by the stimulation of the ventral tegmentum (VT) were studied in 72 male rats of two lines, LC2-Hi and LC2-Lo, genetically selected for high and low rates of lateral hypothalamic self-stimulation, respectively. LC2-Lo rats were more sensitive to acute peripheral pain and developed a stronger analgesia than their LC2-Hi counterparts. In order to assess the pharmacological substrate of ventral tegmental stimulation-induced analgesia (VT-SIA), the effects of amphetamine (AMP, 21 animals), naloxone (NX, 24 animals) and parachlorophenylalanine (PCPA, 27 animals) injections were studied. VT-SIA was found to be clearly decreased by PCPA, slightly decreased by AMP and not significantly affected by NX. Ventral tegmental self-stimulation (VTSS) was increased by PCPA treatment. The comparison of VTSS and VT-SIA did not reveal any correlation between both phenomena. These data suggest that VT-SIA may be mediated by serotonin while catecholamines may have a modulatory role in this analgesia and that VTSS and VT-SIA seem to be governed by different neuronal systems.