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PubMed2002

Distal and proximal pre-exposure to ethanol in the place conditioning task: tolerance to aversive effect, sensitization to activating effect, but no change in rewarding effect.

RATIONALE: The literature offers many examples of tolerance to ethanol's inhibitory/depressant effects and sensitization to its activating effects. There are also many examples of tolerance to ethanol's aversive effects as measured in the conditioned taste aversion and conditioned place aversion (CPA) procedures. However, there are very few demonstrations of either tolerance or sensitization to ethanol's rewarding or reinforcing effects. OBJECTIVE: The present studies were designed to examine effects of two forms of ethanol pre-exposure (distal or proximal) on ethanol's rewarding and aversive effects as indexed by the place conditioning procedure. METHOD: Male inbred (DBA/2J) mice were exposed to ethanol (2 g/kg IP) in an unbiased place conditioning procedure that normally produces either conditioned place preference (CPP) (ethanol injection before CS exposure) or CPA (ethanol injection after CS exposure). In the distal pre-exposure studies (experiments 1 and 2), mice initially received a series of four ethanol injections (0, 2, or 4 g/kg) in the home cage at 48-h intervals during the week before place conditioning. In the proximal pre-exposure studies (experiments 3-4), mice were injected with ethanol 65 min before (experimental groups) or 65 min after (control groups) each paired ethanol injection on CS+ trials. RESULTS: Distal pre-exposure produced a robust sensitization to ethanol's activating effect, whereas proximal pre-exposure generally reduced the activation normally produced by the paired ethanol injection. Both forms of pre-exposure interfered with CPA, but had no effect on CPP. CONCLUSIONS: These studies suggest that both forms of pre-exposure reduced ethanol's aversive effect, but had no impact on ethanol's rewarding effect. In general, the detrimental effects of pre-exposure on CPA are explained best in terms of a reduction in ethanol's efficacy as an aversive unconditioned stimulus (i.e. tolerance), although explanations based on other types of associative interference are also possible. The failure to affect CPP with pre-exposure treatments that reduced or eliminated CPA suggests that these behaviors are mediated by independent, motivationally opposite effects of ethanol. Moreover, these results indicate dissociation between sensitization to ethanol's locomotor activating effect and changes in its rewarding effect. To the extent that motivational processes measured by CPP and CPA normally contribute to ethanol drinking, the present findings suggest that increases in ethanol intake seen after chronic ethanol exposure are more likely caused by tolerance to ethanol's aversive effect rather than sensitization to its rewarding or reinforcing effect.

Animals↗

PubMed2002

The melanocortin receptor agonist MTII augments the rewarding effect of amphetamine in ad-libitum-fed and food-restricted rats.

RATIONALE: Numerous forms of evidence support a functional association between drug-seeking and ingestive behavior. One example is the augmentation of rewarding and cellular-activating effects of abused drugs by chronic food restriction. Within the past several years, a variety of orexigenic and anorexigenic neuropeptides that mediate adaptive responses to changes in energy balance and body weight have been identified. The involvement of these neuropeptidergic signaling systems in the modulation of drug reward has received little experimental attention. alpha-Melanocyte-stimulating hormone (alpha-MSH) and agouti-related protein, which act as agonist and antagonist, respectively, at melanocortin receptors (MCRs), are of particular interest because of their neuroanatomical distribution and opponent actions at a common receptor type. OBJECTIVES: The objective of this study was to determine whether lateral ventricular (i.c.v.) injections of the MCR agonist MTII and MCR antagonist SHU9119 at doses that decrease and increase food intake, respectively, modify the rewarding effect of amphetamine. METHODS: The rewarding effect of amphetamine was measured in terms of its ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequency method. The modulatory effects of MTII and SHU9119 were evaluated by preceding i.c.v. amphetamine injection with i.c.v. injection of one of these MCR ligands or vehicle. Tests were conducted in both ad-libitum-fed and food-restricted subjects. RESULTS: SHU9119, the agouti-related protein-like antagonist, markedly increased overnight food intake of ad-libitum-fm-fed rats following i.c.v. injection of 1.0 microg and 0.5 microg. However, these injections had no effect on thresholds for LHSS tested 25 min or 60 min post-injection, nor did they alter the threshold-lowering effect of amphetamine (50 microg) tested 25 min, 100 min, or 24 h post-injection. MTII, the alpha-MSH-like agonist, suppressed overnight food intake of ad-libitum-fed rats following i.c.v. injection of 1.0 microg. MTII had no effect on thresholds for LHSS tested 60 min post-injection. However, this MCR agonist potentiated the threshold-lowering effect of amphetamine tested 100 min but not 24 h post-injection. This effect was evident in both ad-libitum-fed and food-restricted rats. CONCLUSIONS: These results indicate that agonist activity at MCRs potentiates amphetamine reward and that the anorexigenic neuropeptide alpha-MSH may exert this effect physiologically.

Amphetamine↗

PubMed2002

Effects of the D(3) dopamine receptor antagonist, U99194A, on brain stimulation and d-amphetamine reward, motor activity, and c-fos expression in ad libitum fed and food-restricted rats.

RATIONALE: Previous studies indicate that the D(3) dopamine (DA) receptor is preferentially expressed in limbic forebrain DA terminal areas and may mediate functional effects opposite those of the D(1) and D(2) receptor types. However, the locations of the D(3) receptors that regulate behavior, and the range of behavioral functions regulated, are not clear. OBJECTIVE: The objective of this study was to evaluate behavioral and cellular effects of the preferential D(3) dopamine receptor antagonist, U99194A. METHODS: In experiment 1, the rewarding effect of U99194A (5.0, 10.0 and 20.0 mg/kg, SC) was measured in terms of its ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) in ad libitum fed rats. To amplify a possibly weak reward signal, testing was also conducted in food-restricted rats. The ability of U99194A to alter the threshold-lowering effect of d-amphetamine was also assessed. In experiment 2, effects of U99194A on horizontal and vertical motor activity were compared in ad libitum fed and food-restricted rats. In experiment 3, effects of a behaviorally active dose of U99194A (5.0 mg/kg) on brain c-fos expression were measured and compared to those produced by d-amphetamine (0.5 mg/kg, IP). In experiment 4, the motor and cellular activating effects of U99194A were challenged with the D(1) dopamine receptor antagonist, SCH-23390 (0.1 mg/kg). RESULTS: U99194A displayed no rewarding efficacy in the LHSS paradigm. U99194A did, however, augment the rewarding effect of d-amphetamine. U99194A also produced a motor activating effect, reversible by SCH-23390, which was greater in food-restricted than ad libitum fed rats. The pattern and intensity of fos-like immunoreactivity (FLI) induced by U99194A was similar to that produced by d-amphetamine and was blocked, in caudate-putamen and nucleus accumbens, by SCH-23390. CONCLUSIONS: These results indicate that U99194A has psychostimulant-like effects on motor activity and striatal c-fos expression that are dependent upon the D(1) DA receptor. However, doses of U99194A that are adequate to stimulate motor activity and c-fos expression in striatal and limbic structures do not possess direct rewarding effects in the LHSS paradigm. Overall, these results seem consistent with the hypothesis that D(3) antagonism enhances D(1)/D(2) mediated signaling with behavioral effects dependent on both the density of D(3) receptors and the prevailing level of DA transmission in particular brain regions.

Animals↗

PubMed2003

The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor.

RATIONALE: Within the mammalian ventral tegmental area (VTA), nicotine produces both aversive and rewarding motivational effects. However, the specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes responsible for these effects are not clearly understood. OBJECTIVES: In the present study, we challenged the motivational effects of nicotine directly in the VTA with nAChR subunit specific antagonists. METHODS: Using an unbiased place-conditioning procedure as a behavioural assay, we performed bilateral microinfusions of nicotine over a wide range of concentrations (0.008, 8, 24 and 48 nmol/0.5 microl) and challenged the aversive and reinforcing behavioural effects of these nicotine doses with co-administration of di-hydro-beta-erythroidine (DHbetaE) (5 or 50 nmol/0.5 microl), a nAChR antagonist with higher relative affinity for the alpha4beta2 nAChR subunit, methyllycaconitine citrate (MLA) (0.4 or 4 nmol/0.5 microl), a nAChR antagonist that displays greater relative affinity for the alpha7 nAChR, and the NMDA receptor antagonist, d-2-amino-7-phosphoheptanoic acid (AP-7; 18 nmol/0.5 microl). RESULTS: The alpha4beta2 antagonist DHbetaE blocked both the rewarding and aversive properties of intra-VTA nicotine. However, the alpha7 antagonist MLA blocked nicotine reward and switched the motivational valence of higher doses of nicotine (8-48 nmol/0.5 microl) from rewarding to aversive. The NMDA antagonist AP-7 blocked both the aversive and rewarding effects of intra-VTA nicotine. CONCLUSIONS: These results suggest a functional dissociation between nAChR neural substrates within the VTA that mediate the bivalent motivational properties of nicotine and further suggest that nicotine may produce its motivational effects through a glutamatergic mechanism.

2-Amino-5-phosphonovalerate↗

PubMed2004

Blockade of substantia nigra dopamine D1 receptors reduces intravenous cocaine reward in rats.

RATIONALE: We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia nigra (SN)--not usually considered part of reward circuitry--might have similar effects. OBJECTIVE: To test the hypothesis that blockade of dopamine D1 receptors in the SN reduces the rewarding effects of cocaine. METHODS: Twenty one rats were prepared with intravenous catheters and with bilateral guide cannulae implanted such that injections could be made directly into the SN or just dorsal to the SN. The rats were trained to self-administer intravenous cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR1) schedule of reinforcement. After stable responding developed, 13 of the animals were tested following pretreatment with bilateral microinjections of SCH 23390 at doses of 0, 1, 2 or 4 microg/0.5 microl into the SN and 8 were tested with injections of 0 microg or 4 microg/0.5 microl into a site 2 mm dorsal to the SN site. RESULTS: Microinjections of SCH 23390 in the SN significantly increased rates of cocaine self-administration, while injections dorsal to SN had no significant effect on responding. CONCLUSIONS: These data suggest that blockade of dendritically released DA in the SN reduces the rewarding effects of cocaine. These findings complement accumulating evidence that the rewarding effects of cocaine are not restricted to the drug's ability to elevate dopamine levels in the nucleus accumbens.

Animals↗

PubMed2004

Metabotropic glutamate 5 receptor blockade may attenuate cocaine self-administration by decreasing brain reward function in rats.

RATIONALE: Evidence is accumulating that metabotropic glutamate 5 (mGlu5) receptors play an important role in regulating the reinforcing actions of drugs of abuse. OBJECTIVES: We examined the effects of the mGlu5 receptor antagonist MPEP on cocaine consumption and cocaine-enhanced brain reward function in rats. METHODS: Cocaine consumption was measured in rats with 1 h (short-access; ShA) or 6 h (long-access; LgA) daily access to intravenous cocaine (0.25 mg/infusion) self-administration. Cocaine-enhanced brain reward function was measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. RESULTS: Cocaine consumption remained stable and unaltered over successive self-administration sessions in ShA rats. In contrast, cocaine consumption progressively "escalated" in LgA rats. MPEP (1--9 mg/kg) dose-dependently decreased responding similarly in ShA and LgA rats. These data suggest that mGlu5 receptors regulate the reinforcing properties of cocaine, and that this action of mGlu5 receptors is independent of the escalation in consumption associated with extended access to cocaine self-administration. MPEP doses (1--9 mg/kg) that decreased cocaine self-administration elevated brain reward thresholds to a similar degree in cocaine- and vehicle-treated rats, indicating that MPEP induced a negative affective state. The additive effects of MPEP and cocaine on thresholds resulted in attenuation of the magnitude of cocaine-induced (10 mg/kg) lowering of ICSS thresholds. CONCLUSIONS: Overall, mGlu5 receptors appear to play an important role in regulating cocaine consumption, and also in regulating brain reward function. Further, it is likely that blockade of mGlu5 receptors may attenuate cocaine consumption, at least in part, by decreasing the baseline activity of brain reward circuitries.

Animals↗

PubMed2006

Effects of endocannabinoid neurotransmission modulators on brain stimulation reward.

RATIONALE: The endogenous cannabinoid system is responsive to the neurobiological actions of Delta9-tetrahydrocannabinol (THC) and other cannabinoid ligands. While numerous studies have focused on the behavioral and pharmacological effects of THC and cannabinoid agonists in experimental animals, most recent work focuses on compounds that modulate endocannabinoid neurotransmission. However, the relevant studies concerning the ability of endocannabinoid modulators to modify reward processes in experimental animals remain rather scarce. OBJECTIVES: The present study examined the effects of drugs modulating endocannabinoid neurotransmission on brain reward function using the rate-frequency curve shift paradigm of intracranial self-stimulation (ICSS). METHODS: Animals were implanted with electrodes into the medial forebrain bundle (MFB). After brain stimulation reward thresholds stabilized, rats received intraperitoneal injections of the fatty acid amide hydrolase (FAAH) inhibitors phenylmethylsulfonyl fluoride (PMSF) (0, 15, 30, and 60 mg/kg) and URB-597 (0, 0.3, 1, and 3 mg/kg) and the selective anandamide reuptake inhibitor OMDM-2 (0, 3, 10, and 30 mg/kg). RESULTS: The highest dose of URB-597 and OMDM-2 significantly increased the threshold frequency required for MFB ICSS, while PMSF increased the threshold frequency in all doses tested. The cannabinoid 1 (CB1) receptor antagonist SR141716A reversed the actions of URB-597 and OMDM-2, but not PMSF, without affecting reward thresholds by itself. CONCLUSIONS: These results indicate that under the present experimental conditions endocannabinoid modulators do not exhibit reinforcing properties, but rather have inhibitory influence on reward processes. The anhedonic effects of URB-597 and OMDM-2, but not PMSF, observed at the highest doses in this study are probably mediated through direct CB1 receptor stimulation.

Amidohydrolases↗

PubMed2000

Conditioned place preference: what does it add to our preclinical understanding of drug reward?

RATIONALE: Among the various experimental protocols that have been used to measure drug reward in laboratory animals, conditioned place preference (CPP) has been one of the most popular. However, a number of controversial issues have surrounded the use of this experimental protocol. OBJECTIVE: The present review provides a theoretical overview of some critical issues relevant to CPP. The advantages and limitations of CPP are also covered. RESULTS: Based on modern and traditional theoretical formulations of Pavlovian conditioning, CPP appears to reflect a preference for a context due to the contiguous association between the context and a drug stimulus. Within this theoretical framework, it seems clear that CPP measures a learning process that is fundamentally distinct from drug self-administration. The main advantages of CPP are that it: (1) tests animals in a drug-free state; (2) is sensitive to both reward and aversion; (3) allows for simultaneous determination of CPP and locomotor activity; (4) is adaptable to a variety of species; (5) typically yields dose-effect curves that are monophasic rather than biphasic; and (6) has utility in probing the neural circuits involved in drug reward. The main limitations of CPP are that it: (1) is subject to interpretation based on the notion of novelty seeking; (2) is cumbersome for providing the graded dose-effect curves needed for answering some pharmacological questions; (3) is difficult to interpret when animals prefer one context prior to drug conditioning; and (4) lacks face validity as an experimental protocol of drug reward in humans. CONCLUSION: Despite some limitations, CPP provides unique information about the rewarding effect of contextual cues associated with a drug stimulus.

Animals↗

PubMed2001

Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior.

RATIONALE: Following chronic cocaine self-administration and extinction, lesions of the basolateral amygdala (BLA) will significantly attenuate responding for secondary reward (tone + light previously paired with cocaine), without disrupting lever responding for primary reward. However, the specific neurotransmitters involved in conditioned reinstatement remain to be determined. OBJECTIVE: In the present study, we examined possible receptor substrates of amygdalar regulation of conditioned reinstatement after chronic cocaine self-administration. METHODS: Rats were allowed 2 weeks of 3-h daily sessions of cocaine self-administration along a fixed ratio (FR) 1 schedule. After 1 week of daily 3-h extinction sessions in which no programmed consequences occurred, selective antagonists of glutamate or dopamine (DA) receptors were bilaterally infused at single doses into the BLA prior to testing for a cocaine-conditioned reward (tone + light). Following three more days of extinction trials, receptor antagonist effects on reinstatement of cocaine self-administration in the absence of the conditioned stimulus were determined. RESULTS: Infusion of an NMDA receptor antagonist (AP-5, 1.97 micrograms/side), a kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (CNQX, 0.83 microgram/side), or both drugs together had no significant effects on conditioned reward or reinstatement of cocaine self-administration. In contrast, infusion of a DA D1 receptor antagonist (SCH-23390, 2 micrograms/side) or a combination of SCH-23390 and a DA D2/D3 receptor antagonist (raclopride, 5 micrograms/side) significantly reduced responding for conditioned reward, but did not affect cocaine self-administration. Raclopride alone was without effect on either test day. CONCLUSIONS: These results suggest that conditioned reinstatement of drug-seeking behavior is dependent on amygdalar D1 receptors.

2-Amino-5-phosphonovalerate↗

PubMed2001

Rewarding and locomotor-activating effects of direct dopamine receptor agonists are augmented by chronic food restriction in rats.

RATIONALE: Previous studies indicate that chronic food restriction augments the rewarding and motor-activating effects of diverse drugs of abuse. The drugs that have so far proved susceptible to the augmenting effect of food restriction all increase synaptic concentrations of dopamine (DA). It is not known whether behavioral effects of selective, direct DA receptor agonists are also subject to the augmenting effect of food restriction. OBJECTIVES: The first objective of this study was to investigate whether the rewarding and locomotor-activating effects of the D1 agonist, A77636, and the D2 agonist, quinpirole are augmented by chronic food restriction. The second purpose was to investigate whether the augmented rewarding and locomotor-activating effects of d-amphetamine in food-restricted rats are reversed by the D1 antagonist, SCH23390. METHODS: Rewarding effects of drugs were measured in terms of their ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequency method. Locomotor-activating effects were measured in terms of the number of midline crossings exhibited by rats in a shuttle apparatus. RESULTS: A77636 (1.0 and 2.5 mg/kg, i.p.) produced a greater threshold-lowering effect in food-restricted than ad libitum fed rats but produced variable effects on locomotor activity with no difference between groups. Quinpirole (0.2 and 0.5 mg/kg, i.p.) produced a marginally greater threshold-lowering effect in food-restricted rats and a dramatic locomotor response that was exclusive to food-restricted rats. The D1 antagonist, SCH23390, at a dose of 0.01 mg/kg (i.p.), had no effect on the lowering of LHSS threshold by amphetamine (0.5 mg/kg, i.p.) in ad libitum fed rats but blocked the augmentation otherwise observed in food-restricted rats. SCH23390, at a dose of 0.025 mg/kg, had no effect on locomotor activity induced by amphetamine (0.5 mg/kg) in ad libitum fed rats but blocked the augmentation otherwise observed in food-restricted rats. CONCLUSIONS: These results indicate that the augmentation of reward by food restriction extends to drugs that bypass the DA terminal and act postsynaptically. When taken together with prior immunohistochemical and behavioral findings, these results suggest that food restriction may increase the "enabling" effect of the D1 receptor on DA-mediated behaviors.

Adamantane↗

PubMed1998

Effects of excitotoxic lesions of the rat ventral striatum on the perception of reward cost.

This study examined the possibility that lesions of the nucleus accumbens in rats impair the perception of the "cost of reward", as defined by the number of operant responses needed to obtain a food pellet. In a first experiment, visual cues indicated the cost of reward under a multiple-ratio schedule of reinforcement. In a second experiment, the number of lever presses required for each reward incremented with each trial in a progressive-ratio schedule of reinforcement. Lesions of the nucleus accumbens altered the behavioral response to the increasing cost of reward when there was an absence of external cues. There was no change in the ability of the lesioned rats to respond to visual cues that indicated reward availability. The results are considered in terms of the traditional idea of the nucleus accumbens as a limbic-motor interface: it is suggested that, if the nucleus accumbens serves such a function, it is limited to only some contexts.

Animals↗

PubMed2006

The interactive influences of friend deviance and reward dominance on the development of externalizing behavior during middle adolescence.

This study investigated the interactive effects of friend deviance and reward dominance on the development of externalizing behavior of adolescents in the Child Development Project. Reward dominance was assessed at age 16 by performance on a computer-presented card-playing game in which participants had the choice of either continuing or discontinuing the game as the likelihood of reward decreased and the likelihood of punishment increased. At ages 14 and 16, friend deviance and externalizing behavior were assessed through self-report. As expected, based on motivational balance and response modulation theories, path analysis revealed that age 14 friend deviance predicted age 16 externalizing behavior controlling for age 14 externalizing behavior. Reward dominance was a significant moderator of the relationship between friend deviance and externalizing behavior. The contributions of deviant friends to the development of externalizing behavior were enhanced by adolescents' reward dominance.

Adolescent↗

PubMed2004

The neural circuitry of reward and its relevance to psychiatric disorders.

Scientific interest in how the brain processes reward has burgeoned during the past 50 years since the discovery that rats will do tasks such as pressing a lever to obtain electrical stimulation of the brain. This interest was additionally encouraged by the observation of an association between reward and dopamine activity in the mesocorticolimbic system. In this article, we will discuss the complex nature of reward processing and recent animal studies and human functional neuroimaging studies to elucidate the current understanding of the neural substrates of reward processing and its components. Lastly, we will review recent theoretical and empirical work investigating the role of brain reward circuitry in several psychiatric disorders, including substance use disorders, schizophrenia, pathologic gambling, major depressive disorder, and attention-deficit/hyperactivity disorder.

Animals↗

PubMed1983

Two types of medial hypothalamic inhibition of lateral hypothalamic reward.

Electrode-implanted rats pressed a lever to self-stimulate a reward mechanism in their lateral hypothalamus (LH) each time with a brief train of pulses. Interdigitation of a medial hypothalamus (MH) train into the ipsilateral LH train inhibited the reward as indicated by a reduced lever pressing rate. Such interdigitation into the contralateral LH train resulted in only a minimal inhibition accounted for by an across-midline current spread, thus indicating only an ipsilateral MH-to-LH route for inhibiting reward. By varying the phase of interdigitation according to a pulse-pair technique (cf. 20), the time course of this ipsilateral reward inhibition proved bimodal. The peripheral administration of strychnine, a glycine transmitter antagonist, resulted in disinhibition of the fast rising, fast decay (0.1-2.0 ms) intervals, while peripheral administration of picrotoxin, a GABA transmitter antagonist, increased bar pressing only at the slow rising, slow decay (2-20 ms) intervals. The placement of the MH electrodes was then varied dorsoventrally and the strength of the MH current was reduced to minimize dorsal-ventral current spread. From the resulting differential reductions in the two modes it was inferred that the neural elements in the MH responsible for short duration inhibitory effects on LH reward are concentrated more dorsally whereas those responsible for the longer duration inhibitory effects are concentrated more ventrally. These findings demonstrate the relevance of the pulse-pair technique for visualizing congruences between overt behavior and underlying neurophysiological, neuroanatomical and molecular events.

Animals↗

PubMed1985

Learning and integration of rewarding and aversive stimuli in the rat lateral hypothalamus.

Single neuron activity was recorded in the lateral hypothalamus (LHA) and lateral preoptic-anterior hypothalamic area (IPOA-AHA) of the rat during discrimination learning of cue tones that predicted glucose or intracranial self-stimulation as rewarding stimuli, or electric shock or tail pinch as aversive stimuli, using identical behavior, licking. Rewarding and aversive stimuli had opposite effects on the same LHA neurons, but had the same effects on IPOA-AHA neurons. Neurons in the LHA that differentiated between reward and aversion acquired discrimination of the respective cue tones, while IPOA-AHA neurons responded in the same way to cue tones whether they preceded reward or aversion. The results suggest reward- and aversion-related integrative functions in the LHA and arousal or attentional functions in the IPOA-AHA.

Animals↗

PubMed1994

Spatial, movement- and reward-sensitive discharge by medial ventral striatum neurons of rats.

Previous behavioral and acute electrophysiological data have lead researchers to speculate that the nucleus accumbens integrates limbic, reward and motor information. The present study examined the behavioral correlates to single unit activity of the nucleus accumbens and surrounding ventral striatum as a means of evaluating the integrative functioning of this region in an awake animal. Medial ventral striatum (mVS) activity was recorded as rats completed multiple trials on an eight arm radial maze. Neuronal activity was found to correlate with spatial, reward- and movement-related behavioral conditions. While the majority of cells demonstrated correlates of a single type (i.e. either spatial or reward correlates), 6 cells encoded multiple correlates of different types (i.e. spatial and reward correlates). The data suggests that this integrative process can be active both at the level of the individual neuron, and at the structural level. These results are consistent with the hypothesis that the mVS integrates spatial and reward-related information, which in turn influences voluntary motor output structures in order to achieve accurate navigational behavior.

Animals↗

PubMed1995

Curve-shift analysis of self-stimulation in food-restricted rats: relationship between daily meal, plasma corticosterone and reward sensitization.

Chronic food restriction lowers the threshold for lateral hypothalamic electrical self-stimulation (LHSS). This effect has previously been interpreted to reflect a sensitization of reward. In the present study a curve-shift method was used to explicitly differentiate effects of food restriction on brain stimulation rewarding efficacy and performance. Food restriction consistently shifted rate-frequency curves to the left, lowering the M-50 and Theta-0 parameters of rewarding efficacy. Asymptotic rates of reinforcement and slopes of rate-frequency functions were unaffected, confirming that food restriction does not facilitate LHSS by enhancing performance. In this and previous studies, LHSS in food-restricted rats was measured in the period immediately preceding the daily meal when hunger (i.e., period since last meal) and plasma corticosterone are at peak levels. In the light of evidence that corticosterone may regulate sensitivity of the mesolimbic dopamine pathway and account for the sensitizing effect of stress on psychomotor effects of opiates and stimulants, LHSS and corticosterone were measured in the immediate pre-and post-meal periods. While all food-restricted rats displayed elevated corticosterone levels in the pre-meal period and generally displayed a decline to control levels in the post-meal period, the sensitization of reward was not reversed in the post-meal period. These results indicate that chronic food restriction produces a sensitization of reward that does not depend upon the acute state of hunger that precedes the daily meal and does not vary with dynamic changes in plasma corticosterone level.

Animals↗

PubMed1996

Estimates of the axonal refractory period of midbrain dopamine neurons: their relevance to brain stimulation reward.

Psychophysical studies have shown that the directly activated neurons subserving the rewarding effect produced by electrical stimulation of the medial forebrain bundle (MFB) have refractory periods (RPs) shorter than those of dopaminergic (DA) neurons: this suggests that the directly stimulated substrate for the rewarding effect does not include DA neurons. Comparison of RP estimates. however, is difficult since those of DA neurons were obtained with the standard electrophysiological technique that characterizes cell body/initial segment rather than the directly stimulated axonal segment. Using electrophysiological recording techniques in urethane anesthetized rats, we re-estimated and compared the RP of DA neurons that project to the MFB and the ventral striatum (VST) with two stimulation procedures: one that characterizes the axonal segment near the stimulation electrode and the standard one that characterizes the cell body/initial segment near the recording electrode. Results showed that DA axonal RPs range from 1.0 to 2.2 ms, whereas cell body/initial segment RPs range from 1.0 to 3.0 ms. The axonal RP was equal to or shorter (mean difference = 0.22 ms, n = 15) than the cell body/initial segment RP. Axonal RP estimates for MFB sites range from 1.3 to 2.1 ms. values that slightly overlap with the late recovery from refractoriness reported in psychophysical studies for reward-relevant neurons. Axonal RP estimates obtained for VST sites were very similar (mean = 1.66, LH and 1.62 ms, VST) suggesting that the excitability of DA axons does not differ along their path. These results further support the hypothesis that DA axons are unlikely to constitute a major component of the directly-stimulated reward-relevant axons in the MFB. They also suggest that the direct contribution of DA axons to reward produced by VST stimulation is more important than by the MFB.

Action Potentials↗