Dissociations between appetitive and consummatory responses by pharmacological manipulations of reward-relevant brain regions.

Appetitive behaviors of rats were monitored in a runway situation following central infusions of neuroactive substances into brain areas implicated in electrical self-stimulation. Microinjections of the dopamine antagonist cis-flupentixol or the cholinergic antagonist atropine into the nucleus accumbens (Acb) severely reduced the approach speed and anticipatory shuttlebox activity while leaving the consumption of the 20% sucrose reward intact. Microinjections of GABA into the ventral segmental area (VTA), pedunculopontine segmental nucleus (PPTg), and oral pontine reticular nucleus (PnO) also severely disrupted approach without decreasing consumption. The highest doses of atropine into the VTA, PPTg, and PnO disrupted both consummatory and approach responses equally. The results indicate that modulation of various neurochemistries along the trajectory of the self-stimulation system has stronger effects on appetitive approach than consummatory motivation. The implications for understanding appetitive-approach motivation in the brain are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preparation and in vitro release studies of ibuprofen-loaded films and microspheres made from graft copolymers of poly(L-lactic acid) on acrylic backbones

Several studies have shown that the anterior pretectal nucleus (APtN) is involved in descending inhibitory pathways that control noxious inputs to the spinal cord and that it may participate in the normal physiological response to noxious stimulation. Among other brain regions known to send inputs to the APtN, the dorsal column nuclei (DCN), pedunculopontine tegmental nucleus (PPTg), deep mesencephalon (DpMe), and dorsal raphe nucleus (DRN) are structures also known to be involved in antinociception. In the present study, the effects of stimulating these structures on the latency of the tail withdrawal reflex from noxious heating of the skin (tail flick test) were examined in rats in which saline or hyperbaric lidocaine (5%) was previously microinjected into the APtN. Brief stimulation of the PPTg, DpMe or DRN, but not the DCN, strongly depressed the tail flick reflex. The antinociceptive effect of stimulating the DRN, but not the PPTg or DpMe was significantly reduced, but not abolished, by the prior administration of the local anaesthetic into the APtN. The antinociception induced by stimulation of the PPTg or DpMe, therefore, is unlikely to depend on connections between these structures and the APtN. Similar inhibition of the effect of stimulating the DRN was obtained from rats previously microinjected with naloxone (2.7 nmol) or methysergide (2 nmol) into the APtN. Strongly labelled cells were identified in the DRN following microinjection of the fluorescent tracer Fast Blue into the APtN. These results indicate that the APtN may participate as a relay station through which the DRN partly modulates spinal nociceptive messages. In addition, they also indicate that endogenous opioid and serotonin can participate as neuromodulators of the DRN-APtN connection.     

Sensitivity of brain sites to the inhibitory effect on alcohol intake of the tachykinin aminosenktide

The present study evaluated the sensitivity of several brain sites to the inhibitory effect of the tachykinin (TK) NK-3 receptor agonist aminosenktide (NH2-SENK) on 10% ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring rats. Attention was focused on limbic structures involved in alcohol-seeking behavior and endowed with TK NK-3 receptors. NH2-SENK was bilaterally injected into the shell of the nucleus accumbens (NACC), the medial amygdala (AMY), the dorsal hippocampus (HIPP), the ventral tegmental area (VTA), the bed nucleus of the stria terminalis (BNST), the lateral hypothalamus (LH), and the nucleus basalis magnocellularis (NBM). NH2-SENK (injected up to 25-75 ng/site) into the NACC, AMY, HIPP, and VTA did not significantly modify ethanol intake. Injection of NH2-SENK into the BNST reduced ethanol intake at doses of 25 ng/site or higher, but the same doses also reduced water intake in water-deprived rats and food intake in food-deprived rats. Injection of NH2-SENK into the LH or the NBM at doses of 0.5, 5, or 25 ng/site inhibited 10% ethanol intake even at the lowest dose tested without affecting either food or water consumption in deprived animals. Present results indicate that the LH and the NBM are highly sensitive to the inhibitory effect of the TK NK-3 receptor agonist NH2-SENK on ethanol intake. TK peptides have been shown to evoke conditioned place preference following injection in the LH or the NBM, suggesting that in these brain sites the effect of TK agonists on ethanol intake might be due to interference with reward processes.     

Dopamine depletion reorganizes projections from the nucleus accumbens and ventral pallidum that mediate opioid-induced motor activity

Motor activity elicited pharmacologically from the nucleus accumbens by the mu-opioid receptor agonist D-Ala-Tyr-Gly-NMePhe-Gly-OH (DAMGO) is augmented in rats sustaining dopamine depletions. GABAergic projections from the nucleus accumbens to ventral pallidum and ventral tegmental area (VTA) are involved because stimulation of GABAB receptors in the VTA (by baclofen) or GABAA receptors in the ventral pallidum (by muscimol) inhibit the motor response induced by the microinjection of DAMGO into the nucleus accumbens. The present study was done to determine which of these projections is mediating the augmented DAMGO-induced motor activity that follows 6-hydroxydopamine lesions of the nucleus accumbens. The inhibition of DAMGO-induced activation by pallidal injections of muscimol was markedly attenuated in lesioned animals, whereas the inhibition by VTA injections with baclofen was greatly enhanced. A similar switch in emphasis from pallidal to mesencephalic efferents was not observed for dopamine-induced motor activity, because muscimol microinjections inhibited the response elicited by dopamine microinjection into the nucleus accumbens in all subjects. The stimulation of mu-opioid receptors in the ventral pallidum also elicits motor activation, and this is blocked by baclofen microinjection into the VTA. However, after dopamine depletion in the nucleus accumbens, baclofen in the VTA was ineffective in blocking the motor response by DAMGO in the ventral pallidum. These data reveal that dopamine depletion in the nucleus accumbens produces a lesion-induced plasticity that alters the effect of mu-opioid receptor stimulation on efferent projections from the nucleus accumbens and ventral pallidum.     

Neuroanatomical patterns of fos-like immunoreactivity induced by a palatable meal and meal-paired environment in saline- and naltrexone-treated rats

Opioid antagonists block the positive hedonic response to food taste and are potent inhibitors of palatability-driven feeding. However, the specific brain regions within which opioid peptide secretion contributes to the maintenance of palatability-driven feeding have not been clearly established. In the present study, c-Fos immunohistochemistry was used to identify regions rostral to the hindbrain that display cellular activation in response to a palatable meal and the meal-paired environment. Further, it was determined whether any of the cellular responses could be prevented by pretreating animals with naltrexone. Twenty brain regions known to be involved in gustation, appetite and reward functions were examined. Ingestion of the palatable meal (3.0 g of 30% shortening, 20% sucrose and 50% powdered Purina rat chow) increased Fos-like immunoreactivity (FLI) in lateral hypothalamus (LH), ventral tegmentum (VTA) and medial preoptic area (MPOA), and decreased FLI in the habenula (Hab). The meal-paired environment increased FLI in the VTA and nucleus accumbens shell (NAC shell). Naltrexone (1.0 mg/kg, i.p.) did not block consumption of the small meal but did prevent all of the distinctive increases in FLI induced by the meal and meal-paired environment. Since naltrexone, alone, increased FLI in VTA, NAC shell, central amygdala (ceA) and laterodorsal bed nucleus of the stria terminalis (BSTLD), the blunting of ingestion reward by naltrexone may result from direct or transsynaptic activating effects on opponent neuronal activity within this highly interconnected set of structures that mediate and modulate reward.     

Increased ipsilateral expression of Fos following lateral hypothalamic self-stimulation

Immunohistochemical labeling of Fos protein was used to visualize neurons activated by rewarding stimulation of the lateral hypothalamic level of the medial forebrain bundle (MFB). Following training and stabilization of performance, seven rats were allowed to self-stimulate for 1 h prior to anesthesia and perfusion. Brains were then processed for immunohistochemistry. Two control subjects were trained and tested in an identical manner except that the stimulator was disconnected during the final 1 h test. Among the structures showing a greater density of labeled neurons on the stimulated side of the brains of the experimental subjects were the septum, lateral preoptic area (LPO), medial preoptic area, bed nucleus of the stria terminalis, substantia innominata (SI), and the lateral hypothalamus (LH). Several of these structures, the LPO, SI, and LH, have been implicated in MFB self-stimulation by the results of psychophysical, electrophysiological, and lesion studies.     

Electrophysiological characterization of GABAergic neurons in the ventral tegmental area

GABAergic neurons in the ventral tegmental area (VTA) play a primary role in local inhibition of mesocorticolimbic dopamine (DA) neurons but are not physiologically or anatomically well characterized. We used in vivo extracellular and intracellular recordings in the rat VTA to identify a homogeneous population of neurons that were distinguished from DA neurons by their rapid-firing, nonbursting activity (19.1 +/- 1.4 Hz), short-duration action potentials (310 +/- 10 microseconds), EPSP-dependent spontaneous spikes, and lack of spike accommodation to depolarizing current pulses. These non-DA neurons were activated both antidromically and orthodromically by stimulation of the internal capsule (IC; conduction velocity, 2.4 +/- 0.2 m/sec; refractory period, 0.6 +/- 0.1 msec) and were inhibited by stimulation of the nucleus accumbens septi (NAcc). Their firing rate was moderately reduced, and their IC-driven activity was suppressed by microelectrophoretic application or systemic administration of NMDA receptor antagonists. VTA non-DA neurons were recorded intracellularly and showed relatively depolarized resting membrane potentials (-61.9 +/- 1.8 mV) and small action potentials (68.3 +/- 2.1 mV). They were injected with neurobiotin and shown by light microscopic immunocytochemistry to be multipolar cells and by electron microscopy to contain GABA but not the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Neurobiotin-filled dendrites containing GABA received asymmetric excitatory-type synapses from unlabeled terminals and symmetric synapses from terminals that also contained GABA. These findings indicate that VTA non-DA neurons are GABAergic, project to the cortex, and are controlled, in part, by a physiologically relevant NMDA receptor-mediated input from cortical structures and by GABAergic inhibition.     

Anatomical dissociation of the substrates of medial forebrain bundle self-stimulation and exploration.

The purpose of this research was to determine whether brain stimulation reward and exploration are induced by activation of the same set of neurons along the medial forebrain bundle. The behavioral version of the collision test was utilized with electrodes in the lateral hypothalamus (LH) and the ventral tegmental area (VTA). A collision effect obtained between LH and VTA in one behavior at the exclusion of the other was treated as evidence of the involvement of two different sets of fibers. In 4 rats, a collision effect was observed only in self-stimulation, whereas in 1 rat, a collision was obtained in exploration at the exclusion of self-stimulation. Three animals showed no collision in either behavior. These data suggest that coexistence of self-stimulation and exploration following medial forebrain bundle stimulation can be explained by current spread on two different sets of fibers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine tegmental nucleus.

Prepulse inhibition (PPI) of startle is impaired in schizophrenics, which suggests they have disturbances in circuitry that controls PPI. How activity in forebrain circuitry is communicated to the primary startle circuit to modulate PPI was explored. Subpallidal cells innervate the pedunculopontine tegmental nucleus (PPTg). Infusion of the γ-aminobutyric acid antagonist picrotoxin into the subpallidum impaired PPI. In other rats, electrolytic PPTg lesions decreased or eliminated PPI, potentiated startle amplitude, and did not alter habituation. The disruption of PPI correlated significantly with the extent of PPTg damage. PPTg lesions reduced PPI when startle stimuli were weak or intense (104 or 140 db) and when prepulse stimuli ranged from 2 to 17 db above background but were most profound with prepulses 5–8 db above background. The PPTg modulates sensorimotor gating and may process and transmit information from forebrain structures to the primary startle curcuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Agonist-induced desensitization of adenylyl cyclase activity mediated by 5-hydroxytryptamine7 receptors in rat frontocortical astrocytes

A reward-relevant relationship between dopamine projection regions of the ventral tegmental area (VTA) was investigated through the use of brain stimulation reward (BSR) thresholds. Using a rate-free method, changes in VTA BSR thresholds were determined after intracranial injections of the dopamine D1 antagonist, SCH 23390 into the prefrontal cortex (PFC), or the nucleus accumbens (NAcc). Reward thresholds assessed immediately after the infusion of SCH 23390 into the NAcc (0.5 microgram/0.5 microliter/side) were significantly higher than those assessed just after saline infusions, indicating a drug-induced attenuation of the rewarding effects of the brain stimulation. The effects of this dose subsided when tested 24 h later. Conversely, intra-PFC infusions of SCH 23390 at the same dose (0.5 microgram/0.5 microliter/side) resulted in lowered BSR thresholds when rats were tested immediately after infusion. In addition, animals tested 24 h after receiving the lowest dose (0.125 microgram/0.5 microliter/side) demonstrated a robust delayed threshold-lowering effect. These immediate and delayed effects of the intra-PFC dopamine antagonist demonstrate a facilitation of VTA BSR and are consistent with the view that PFC dopamine serves a modulatory role over important reward elements within the NAcc. The deferred effects of intra-prefrontal cortex DA receptor blockade on brain stimulation reward thresholds may reflect adaptive responses of subcortical structures to changes in PFC dopamine neurotransmission. It has been suggested that neural adjustments of this type may underlie long term changes in central nervous system functioning brought about by disease, drug use or behavioral conditioning.     

Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: an in vivo microdialysis study in freely moving rats

In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cholecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accumbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was intensity-dependent at 250-700 microA. NAS Glu and DA levels were each elevated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and homovanillic acid were increased by stimulation at 100-400 Hz. When rats were trained to lever press for mPFC stimulation, the stimulation induced similar elevations of each of the three transmitters to those seen with experimenter-administered stimulation. Perfusion of 1 mM kynurenic acid (Kyn) into either the ventral tegmental area (VTA) or NAS blocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induced by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when perfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence for the existence of a releasable pool of CCK in the NAS originating from the mPFC. Although dopamine is the transmitter most closely linked to reward function, it was CCK that showed frequency-dependent differences in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, coreleased CCK may modulate the impact of the glutamatergic action in this behavior.     

The pedunculopontine tegmental nucleus: where the striatum meets the reticular formation

The pedunculopontine tegmental nucleus (PPTg) contains a population of cholinergic neurons (the Ch5 group) and non-cholinergic neurons. There appears to be functional interdigitation between these two groups, which both have extensive projections. The principal ascending connections are with thalamic nuclei and structures associated with the striatum, including the substantial nigra pars compacta. The descending connections are with a variety of nuclei in the pons, medulla and spinal cord, concerned with autonomic and motor functions. In the past, emphasis has been laid on the role of the PPTg in locomotion and behavioural state control. In this review, we emphasise the role of the PPTg in processing outputs from the striatum. The non-cholinergic neurons receive outflow from both dorsal and vental striatum, and lesions of the PPTg disrupt behaviour associated with each of these. Our review indicates that the PPTg is less concerned with the induction of locomotion and more concerned with relating reinforcement (information about which comes from the ventral striatum) with motor output from the dorsal striatum. The conclusions we draw are: (1) the PPTg is an outflow system for the striatum, but also forms a 'subsidiary circuit', returning information to striatal circuitry; in this, the PPTg has an anatomical organisation that resembles that of the substantia nigra. (2) As well as a role in the mediation of REM sleep, cholinergic PPTg neurons have an important role in the waking state, providing feedback into the thalamus and striatum. (3) The precise function of the computations performed on striatal outflow by the PPTg is uncertain. We discuss whether this function is complementary (parallel to other routes of striatal outflow), integrative (modifying other forms of striatal outflow) or both.     

Lateral hypothalamic stimulation can augment or attenuate nucleus gigantocellularis escape: Evidence for appetite-associated aversion amelioration.

K. Carr and E. E. Coons (see PA, Vol 68:7638 and 3020) found that lateral hypothalamic (LH) stimulation ameliorates the aversiveness of stimulation of pain-implicated nucleus gigantocellularis (NGC), but this finding disagrees with other findings. To resolve this disagreement, we tested whether amelioration is differentially associated with the ability of LH stimulation to support self-stimultion (SS), to support responding to escape LH stimulation (LH escape), or to elicit stimulation-bound feeding (SBF). LH stimulation not yielding SBF always increased responding to escape from NGC stimulation (NGC escape) and was reward-escape in nature in supporting LH escape as well as SS. By contrast, LH stimulation yielding SBF always reduced NGC escape and was purely rewarding in that it only supported SS and never LH escape. In an additional experiment, the anxiolytic diazepam augmented the ability of LH stimulation yielding SBF to reduce NGC escape. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increase of extracellular glutamate and expression of Fos-like immunoreactivity in the ventral tegmental area in response to electrical stimulation of the prefrontal cortex

Electrical stimulation of the medial prefrontal cortex caused glutamate release in the ventral tegmental area (VTA) of freely moving animals. Cathodal stimulation was given through monopolar electrodes in 0.1-ms pulses at an intensity of 300 microA and frequencies of 4-120 Hz. Glutamate was measured in 10-min perfusate samples by HPLC coupled with fluorescence detection following precolumn derivatization with o-phthaldialdehyde/beta-mercaptoethanol. The stimulation-induced glutamate release was frequency dependent and was blocked by the infusion of the sodium channel blocker tetrodotoxin (10 microM) through the dialysis probe. The stimulation also induced bilateral Fos-like immunoreactivity in ventral tegmental neurons, with a significantly greater number of Fos-positive cells on the stimulated side. These findings add to a growing body of evidence suggesting that the medial prefrontal cortex regulates dopamine release in the nucleus accumbens via its projection to dopamine cell bodies in the VTA.     

Strong nuclear factor-kappaB-DNA binding parallels cyclooxygenase-2 gene transcription in aging and in sporadic Alzheimer''s disease superior temporal lobe neocortex

This study investigated the putative role of non-NMDA excitatory amino acid (EAA) receptors in the ventral tegmental area (VTA) for the increase in dopamine (DA) release in the nucleus accumbens (NAC) and behavioral stimulation induced by systemically administered dizocilpine (MK-801). Microdialysis was utilized in freely moving rats implanted with probes in the VTA and NAC. Dialysates from the NAC were analyzed with high-performance liquid chromatography for DA and its metabolites. The VTA was perfused with the AMPA and kainate receptor antagonist CNQX (0.3 or 1 mM) or vehicle. Forty min after onset of CNQX or vehicle perfusion of the VTA, MK-801 (0.1 mg/kg) was injected subcutaneously. Subsequently, typical MK-801 induced behaviors were also assessed in the same animals by direct observation. MK-801 induced hyperlocomotion was associated with a 50% increase of DA levels in NAC dialysates. Both the MK-801 evoked hyperlocomotion and DA release in the NAC was antagonized by CNQX perfusion of the VTA in a concentration-dependent manner. None of the other rated MK-801 evoked behaviors, e.g. head weaving or sniffing, were affected by CNQX perfusion of the VTA. By itself the CNQX or vehicle perfusion of the VTA alone did not affect DA levels in NAC or any of the rated behaviors. These results indicate that MK-801 induced hyperlocomotion and DA release in the NAC are largely elicited within the VTA via activation of non-NMDA EAA receptors, tentatively caused by increased EAA release. Thus, the locomotor stimulation induced by psychotomimetic NMDA receptor antagonists may not only reflect impaired NMDA receptor function, but also enhanced AMPA and/or kainate receptor activation in brain, e.g., in the VTA. In view of their capacity to largely antagonize the behavioral stimulation induced by psychotomimetic drugs, such as MK-801, AMPA, and/or kainate receptor antagonists may possess antipsychotic efficacy.     

The ventral pallidum mediates disruption of prepulse inhibition of the acoustic startle response induced by dopamine agonists, but not by NMDA antagonists

Prepulse inhibition (PPI) of the acoustic startle response is observed when the startling noise pulse is preceded by a weak, non-startling stimulus. PPI has been considered as a measure for sensorimotor gating mechanisms. Disruption of PPI can be found in schizophrenic patients as well as after blockade of NMDA receptors or stimulation of dopamine receptors in rats. The neuronal circuitry which regulates PPI consists of cortico-limbic brain structures where the nucleus accumbens (NAC) plays a key role. The NAC exerts its modulating effects on PPI by way of a projection from the ventral pallidum (VP) to the pedunculopontine tegmental nucleus (PPTg). We recently postulated that the reduction of PPI by intra-NAC infusion of glycine-site NMDA antagonists is not mediated by the VP. We tested here this hypothesis in rats with excitotoxic lesions of the VP which were systemically treated with apomorphine or MK-801 or received intraNAC infusions of dopamine or the glycine-site NMDA antagonist 7-chlorokynurenic acid. Lesioned rats showed a marked deficit in PPI after MK-801 and 7-chlorokynurenate treatment but not after apomorphine or dopamine injection, in contrast to sham-lesioned controls showing deficits in PPI under all conditions. These data provide behavioral evidence for the existence of a pathway which does not include the VP for the mediation of sensorimotor gating deficits. We propose that a direct connection between the NAC and PPTg may be responsible for the effects of NMDA/glycine receptor blockade, whereas the VP is an indispensable relay for the disruptive effects on PPI exerted by the NAC dopamine system.     

Separate neural substrates mediate the motivating and discriminative properties of morphine.

A previous study (T. V. Jaeger & D. van der Kooy, 1993) has implicated a visceral and taste region (parabrachial nucleus), but not mesolimbic dopamine terminal fields (nucleus accumbens), as a substrate for opiate discriminative effects. The authors now show that (a) morphine's discriminative effects in the parabrachial nucleus (PBN) require the activation of opiate receptors; (b) in rats trained to discriminate morphine from saline, infusions of morphine into the ventral tegmental area (VTA) do not generalize to the systemic training condition; (c) infusions of morphine into the PBN, but not the VTA, serve as a stimulus for the acquisition of discrimination learning; and (d) morphine applied to the VTA, but not the PBN, is motivating. The data show that the motivating and discriminative effects of morphine are processed separately by the brain. Further, discriminative drug effects are neither necessary nor sufficient for opiate motivational effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The third five-year survey of fellows (by examination) of the Faculty of Intensive Care, Australian and New Zealand College of Anaesthetists

The activity of the pedunculopontine tegmental nucleus (PPTg) neurons was recorded in three unrestrained cats operantly conditioned to perform a lever-release movement. The movement had to be initiated either rapidly after a (click) stimulus in a simple reaction-time paradigm or had to be delayed after the same stimulus in trials identified by a tone cue. Successful trials were rewarded by a food pellet. A total of 107 neurons were recorded with microelectrodes. Brief spike neurons (mean duration: 0.7 ms) and broad spike neurons (mean duration: 2 ms) presumed to be cholinergic were detected. Of the 73 neurons localized in the PPTg area, 53 had brief spikes and 20 broad spikes. Changes in activity most commonly occurred very early after the stimulus or during the reinforcement process. Most neurons with brief spikes exhibited very early excitation after the stimulus and reinforcement-related activity. These neurons had a mean activity of 23.7 impulses/s in the period preceding the stimulus. The onset of activation after the stimulus had a latency of 8.6+/-6.9 ms (mean+/-SD), with a range of 4-35 ms. In trials where the movement had to be delayed after the stimulus, the early activation disappeared or was considerably reduced, showing that it was context-dependent. A small proportion of neurons with brief spikes initially decreased activity after the stimulus, but with a latency >9 ms. All the neurons with broad spikes, except one, had reinforcement-related activity. Half of them showed exclusively reinforcement-related activity, the other half also early activation after the stimulus. These neurons were about half as active in the period preceding the stimulus occurrence than the neurons with brief spikes. The early context-dependent activation is discussed in relation to the excitatory projection of PPTg neurons on the subthalamic nucleus. The reinforcement-related activity, preferentially evidenced in broad spike neurons presumed to be cholinergic, is speculated to be associated with cholinergic projection of PPTg neurons to the dopaminergic neurons of the substantia nigra. Finally, the role of PPTg in the ongoing control of motor performance and reinforcement processes is discussed in relation to the basal ganglia circuitry.     

Pedunculopontine tegmental nucleus lesions impair stimulus–reward learning in autoshaping and conditioned reinforcement paradigms.

The role of the pedunculopontine tegmental nucleus (PPTg) in stimulus–reward learning was assessed by testing the effects of PPTg lesions on performance in visual autoshaping and conditioned reinforcement (CRf) paradigms. Rats with PPTg lesions were unable to learn an association between a conditioned stimulus (CS) and a primary reward in either paradigm. In the autoshaping experiment, PPTg-lesioned rats approached the CS+ and CS– with equal frequency, and the latencies to respond to the two stimuli did not differ. PPTg lesions also disrupted discriminated approaches to an appetitive CS in the CRf paradigm and completely abolished the acquisition of responding with CRf. These data are discussed in the context of possible cognitive function of the PPTg, particularly in terms of lesion-induced disruptions of attentional processes that are mediated by the thalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the pedunculopontine tegmental nucleus increase sucrose consumption but do not affect discrimination or contrast effects.

Pedunculopontine tegmental nucleus (PPTg) lesions block place preferences to drugs or food only when animals are nondeprived. PPTg lesions also disrupt operant responding, but lesioned rats cannot discriminate active from inactive levers. It is not clear, therefore, whether PPTg lesions block reward or disrupt the ability to differentiate changes in reward magnitude. These hypotheses were tested by measuring sucrose consumption, choice, and contrast effects after PPTg lesions. Both sham and lesioned rats consumed greater amounts of a sucrose solution as the concentration and level of deprivation were increased. Given a choice between 2 solutions, all rats consumed more of the higher concentration. Both groups exhibited contrast effects when the concentration was shifted from 32% to 4% within a session. Somewhat surprisingly, lesions increased sucrose intake when rats were food-restricted. These results suggest that PPTg lesions do not disrupt primary motivation or the ability to evaluate and respond to changes in reward strength. (PsycINFO Database Record (c) 2010 APA, all rights reserved)