CaV channel blockade in the extended amygdala has a delayed effect on the reward efficacy of medial forebrain bundle stimulation.

Previous work in our laboratory has shown that stimulating D2 dopamine receptors in the central sublenticular extended amygdala (SLEAc) can render medial forebrain bundle (MFB) stimulation less rewarding. One of the many ways in which D2 stimulation could affect the activity status of SLEAc neurons is by indirectly blocking calcium ion (Ca) influx through CaV channels. He we directly investigate the effects of blocking CaV channels on the rewarding effect of MFB stimulation.

Toward a systems-oriented approach to the role of the extended amygdala in adaptive responding.

Research into the structure and function of the basal forebrain macrostructure called the extended amygdala (EA) has recently seen considerable growth. This paper reviews that work, with the objectives of identifying underlying themes and developing a common goal towards which investigators of EA function might work. The paper begins with a brief review of the structure and the ontological and phylogenetic origins of the EA.

Comparison of the effects on brain stimulation reward of D1 blockade or D2 stimulation combined with AMPA blockade in the extended amygdala and nucleus accumbens.

This report compares the effects on medial forebrain bundle self-stimulation of injecting into either the sublenticular central extended amygdala (SLEAc) or nucleus accumbens shell (NAcS) the D1 dopamine receptor blocker SCH23390 or the D2 dopamine receptor agonist quinpirole alone or in combination with the AMPA glutamate receptor blocker NBQX. These manipulations all render affected neurons less excitable and therefore are expected to increase the stimulation pulse frequency required to maintain half-maximal response rate (required frequency, or RF). Injections were made ipsilateral and contralateral to the stimulation site but not bilaterally.

Brain stimulation reward is altered by affecting dopamine-glutamate interactions in the central extended amygdala.

This work compares the effects on brain stimulation reward (BSR) when combining D2 dopamine receptor and AMPA glutamate receptor manipulations in the sublenticular central extended amygdala (SLEAc) and the nucleus accumbens shell (NAc shell). Thirty-seven male Long Evans rats received medial forebrain bundle (MFB) stimulation electrodes and bilateral injection guide cannulae aimed at either the SLEAc or the NAc shell. The rate-frequency paradigm was used to assess drug-induced changes in stimulation reward effectiveness and in response rate following 0.

Brain stimulation reward is affected by D2 dopamine receptor manipulations in the extended amygdala but not the nucleus accumbens.

This work examines the effects on brain stimulation reward (BSR) of D1 and D2 dopamine receptor manipulations in the sublenticular central extended amygdala (SLEAc) and the nucleus accumbens shell (NAc). Fifty-three male Long Evans rats received medial forebrain bundle stimulation electrodes and bilateral injection guide cannulae aimed at either the SLEAc or the NAc. The rate-frequency paradigm was used to assess drug-induced changes in stimulation reward effectiveness and in response rate following 0.

GABA receptor agonism in the sublenticular central extended amygdala impairs medial forebrain bundle self-stimulation but GABA blockade does not enhance it.

The sublenticular central extended amygdala (SLEAc), which is important in medial forebrain bundle (MFB) self-stimulation, is heavily populated with GABAergic medium spiny neurons that intercommunicate via local axon collaterals. This study examines the role of GABAergic communication in the SLEAc in MFB self-stimulation. Male Long-Evans rats were given unilateral MFB stimulation electrodes and bilateral injection guide cannulae aimed at the SLEAc.

Muscimol inactivation of the septo-preoptic complex affects medial forebrain bundle self-stimulation only when directed at the complex's ventrolateral components.

Elements of the septo-preoptic basal forebrain complex, particularly the lateral and medial septum, the diagonal band of Broca, and the magnocellular preoptic area, have been linked to medial forebrain bundle (MFB) self-stimulation. This study examines the roles of these areas in MFB self-stimulation by temporarily inactivating them with 25 and 50ng doses of the GABA(A) receptor agonist muscimol. Changes in performance capacity and stimulation reward effectiveness were evaluated with the rate-frequency curve shift paradigm.

Lidocaine inactivation of the ventral pallidum affects responding for brain stimulation reward more than it affects the stimulation's reward value.

The ventral pallidum (VP) supports self-stimulation and has anatomical connections that suggest it could be linked to medial forebrain bundle (MFB) self-stimulation. Dorsal VP appears to be more related to dorsal striatopallidum and thus to cognitive control of movement, while ventral VP appears to be more related to linking motivation to action. In this study we challenged MFB self-stimulation by temporarily inactivating dorsal and ventral VP.

The central extended amygdala network as a proposed circuit underlying reward valuation.

The phenomenon of medial forebrain bundle self-stimulation offers a powerful model of reward-based behavior. In particular, it appears to activate a neural system whose natural function is to compute the survival value or utility of present stimuli and to help orchestrate responses toward those inputs. Although the anatomical identity of this system is as yet unknown, recent descriptions of anatomical macrosystems within the basal forebrain lead to the proposal that it may be largely contained within the central extended amygdala network.

Lidocaine inactivation demonstrates a stronger role for central versus medial extended amygdala in medial forebrain bundle self-stimulation.

Given recent attention to the role of the extended amygdala (EA) in brain reward processes, this study examines the relative contributions of the medial versus central aspects of that forebrain macrostructure to the rewarding effects of medial forebrain bundle (MFB) stimulation. Thirty-one rats were self-stimulated at either the rostral or caudal MFB before and after lidocaine-induced inactivation of an EA target. Relative to non-injection baseline tests, the injection of 0.

Lesions and inactivation implicate dorsolateral hindbrain in MFB self-stimulation.

Two experiments explored the role of the motor nucleus of the trigeminal nerve (Mo5) and surrounding area in the rewarding effects of medial forebrain bundle (MFB) stimulation. In the first, eight rats received serial bilateral lesions of the target region. The reward value of MFB stimulation was assessed at 200, 400, and 800 microA using the rate-frequency curve shift paradigm.

Temporary inactivation of the retrorubral fields decreases the rewarding effect of medial forebrain bundle stimulation.

Prior studies indicate that lesioning the retrorubral fields (RRF) decreases the rewarding effect of medial forebrain bundle (MFB) stimulation, although these studies did not make the RRF their primary target. This study directly investigates the role of the RRF in MFB self-stimulation using transient lidocaine-induced inactivation of target tissue rather than permanent lesioning. In 18 rats with MFB stimulation electrodes, inactivation of the RRF via 0.

Lesions of midline midbrain structures leave medial forebrain bundle self-stimulation intact.

Previous work with psychophysically-based collision methods and pharmacological manipulation suggests a role in medial forebrain bundle (MFB) self-stimulation for neurons lying along the midline between the cerebral hemispheres, in the mid- and/or hindbrain. Also, recently-proposed models of the anatomical substrate for medial forebrain bundle stimulation reward suggest that at least part of the directly-activated axons of this substrate arise from mid- and/or hindbrain somata, bifurcate, and send bilateral projections to the MFB of each hemisphere. Branches of these axons are thought to cross the midline at some point near the ventral tegmental area.

Midbrain periaqueductal lesions do not degrade medial forebrain bundle stimulation reward.

To investigate the possible role of the midbrain central grey and dorsal raphe in medial forebrain bundle (MFB) self-stimulation, 12 rats received monopolar stimulation electrodes in both the lateral hypothalamic and ventral tegmental MFB and an ipsilateral lesioning electrode in either the central grey or dorsal raphe. Baseline rate-frequency data were collected at several currents at each stimulation site until the frequency required to maintain half-maximal responding stabilized and then an electrolytic lesion was made by passing either 20 or 60 s of anodal constant current through the lesioning electrode. Post-lesion rate-frequency data indicated that lesions of the central grey and dorsal raphe had little appreciable effect on the rewarding nature of MFB stimulation.

Lesions of pontomesencephalic cholinergic nuclei do not substantially disrupt the reward value of medial forebrain bundle stimulation.

This study examines the effects of lesioning the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) on the reward effectiveness of medial forebrain bundle (MFB) stimulation. Although the focus is on the effects of unilateral lesions made ipsilateral to stimulation sites in the hypothalamic and ventral tegmental MFB, the effects of contralateral lesions of both targets are also investigated. Reward effectiveness was assessed using the rate-frequency curve shift paradigm.

Destruction of the medial forebrain bundle caudal to the site of stimulation reduces rewarding efficacy but destruction rostrally does not.

Rats with an electrode in the medial forebrain bundle (MFB) in or near the ventral tegmental area and another at the level of the rostral hypothalamus sustained large electrolytic lesions at either the rostral or the caudal electrode. The rewarding efficacy of stimulation through the other electrode was determined before and after the lesion. Massive damage to the MFB in the rostral lateral hypothalamus (LH) generally had little effect on the rewarding efficacy of more caudal stimulation, whereas large lesions in the caudal MFB generally reduced the rewarding efficacy of LH stimulation by 35-60%.

Effects of excitotoxic lesions of the basal forebrain on MFB self-stimulation.

Electrolytic lesions of the anterior medial forebrain bundle (MFB) have been shown to attenuate the rewarding impact of stimulating more caudal MFB sites. In the present study, excitotoxic lesions were employed to determine the relative contribution of somata or fibers of passage contributing to that effect. Changes in reward efficacy were inferred, at three currents, from lateral displacements of the curve relating the rate of responding to the number of stimulation pulses per train.

Self-stimulation of the MFB following parabrachial lesions.

It has been reported previously that the parabrachial region supports robust self-stimulation. In the present study, we determined whether lesions of the parabrachial nucleus (PBN) influence the rewarding effect of medial forebrain bundle (MFB) stimulation. In 10 rats, stimulation electrodes were aimed at the lateral hypothalamus and/or ventral tegmental area and a lesioning electrode aimed at the PBN.

Rewarding effectiveness of caudal MFB stimulation is unaltered following DMH lesions.

The dorsomedial hypothalamus (DMH) has been proposed to be a major part of the neural substrate for self-stimulation of the medial forebrain bundle (MFB). In this report, rate-frequency and rate-current curves were collected from 19 rats with lesions in or around the DMH and stimulation electrodes in or near the caudal MFB. Thirteen rats with lesions of the DMH showed little or no postlesion change in the rewarding effectiveness of caudomedial MFB stimulation.

Effect of current on the maximum possible reward.

Using a 2-lever choice paradigm with concurrent variable interval schedules of reward, it was found that when pulse frequency is increased, the preference-determining rewarding effect of 0.5-s trains of brief cathodal pulses delivered to the medial forebrain bundle of the rat saturates (stops increasing) at values ranging from 200 to 631 pulses/s (pps). Raising the current lowered the saturation frequency, which confirms earlier, more extensive findings showing that the rewarding effect of short trains saturates at pulse frequencies that vary from less than 100 pps to more than 800 pps, depending on the current.

The effects of excitotoxin lesions of the lateral hypothalamus on self-stimulation reward.

Unilateral microinjection into rat lateral hypothalamus (LH) of the excitotoxins ibotenic acid (IBO) and N-methyl-D-aspartic acid (NMDA) produced a local zone of neuronal death but also produced a zone of demyelination. The size of this demyelination zone was related to excitotoxin dose and was smaller than the zone of neuron killing. In behavioral testing, MFB self-stimulation reward and performance were measured with a rate-frequency curve-shift method before and after IBO or NMDA lesions of the LH.

Failure of amygdaloid lesions to increase the threshold for self-stimulation of the lateral hypothalamus and ventral tegmental area.

It has been proposed that the directly stimulated axons underlying the rewarding effect of medial forebrain bundle (MFB) stimulation originate in the forebrain and descend at least as far as the ventral tegmentum. However, little is known about the location of the somata that give rise to these axons. Among the nuclei that contribute fibers to the descending component of the MFB and project past the lateral hypothalamus (LH) and ventral tegmental area (VTA) are cell groups within the amygdaloid complex.

Frequency-response characteristics provide a functional separation between stimulation-bound feeding and self-stimulation.

Many lateral hypothalamic electrodes that support self-stimulation also elicit feeding. Refractory period and conduction velocity estimates for the axons supporting these behaviors appear identical, suggesting that these behaviors may be elicited by stimulation of a common directly activated substrate. However, it is not known if the substrate(s) for the two behaviors integrate activity in directly stimulated axons similarly in controlling their respective behaviors.

Neonatal dopamine depletions spare lateral hypothalamic stimulation reward in adult rats.

Previous research has shown that adult rats sustaining near-total depletions of striatal dopamine (DA) as neonates exhibit few of the profound deficits in ingestion and sensory-motor behavior seen in comparably lesioned adults. This study extends these findings to another realm of DA-related behavior, reward function. In a rate-frequency curve-shift measurement paradigm, reward effectiveness of lateral hypothalamic brain stimulation was shown to be normal in adult rats depleted of brain DA as neonates.

Basal forebrain knife cuts and medial forebrain bundle self-stimulation.

Current autoradiographic and electrophysiological data suggest that fibers coursing from the diagonal band/medial septum and lateral preoptic area through the medial forebrain bundle (MFB) to the midbrain may carry the reward signals generated by lateral hypothalamic stimulation. To test this hypothesis, 40 rats were given a unilateral lateral hypothalamic stimulating electrode and an ipsilateral guide cannula for knife cut transection. In baseline self-stimulation testing, both the animal's capacity to respond for the stimulation and the reward efficacy of the stimulation were measured.