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At least 721 records · Page 40Linked to original sources
PubMed2005

Mu-opioid receptor and CREB activation are required for nicotine reward.

Environmental cues associated with nicotine delivery are an important part of the stimulus that sustains smoking behavior and is often coupled with craving and relapse; however, the neuronal circuitry and molecular substrates underlying this process are still poorly understood. Exposure to an environment previously associated with rewarding properties of nicotine results in an increase of CREB phosphorylation similar to that seen following nicotine administration, and this response is absent in MOR(-/-) mice. Moreover, a single administration of an opioid receptor antagonist, naloxone, blocks both the conditioned molecular response (CREB phosphorylation) and the conditioned behavioral response (nicotine reward) in a place preference paradigm. Lastly, repeated nicotine administration results in increased expression of MORs. However, this effect, along with rewarding properties of nicotine, is blocked in mice with a targeted disruption in the CREB gene. Together, pharmacologic and genetic manipulations indicate that phosphorylation of CREB and upregulation of functional MORs are required for nicotine-conditioned reward.

Analysis of Variance↗
PubMed2004

Individual responses to novelty predict qualitative differences in d-amphetamine-induced open field but not reward-related behaviors in rats.

Differences in the locomotor response of rats to a novel environment (high responders [HR] versus low responders [LR]) have been associated with differences in vulnerability to psychostimulants. In the present study we profiled extensively the behavioral repertoire of HR and LR rats (differentiated on the basis of vertical activity) during exposure to a novel environment and in response to d-amphetamine (d-amp; 1.5 mg/kg, i.p.). Moreover, we ascertained whether HR and LR rats differ in the rewarding effects of medial forebrain bundle electrical self-stimulation and in the ability of d-amp to increase the reinforcing efficacy of self-stimulation. Apart from rearing, HR animals displayed increased moving, sniffing, but decreased standing and yawning compared with LR. Factor analysis revealed a more complex behavioral structure consisting of locomotion, exploration, vertical activity and self-directed behavior for HR compared with LR rats. Qualitative, but not quantitative differences, between the two groups of rats in their behavioral responses to d-amp were found. In particular, a more complex profile mainly characterized by self-directed behavior, locomotion and vertical activity was manifested for HR as compared with LR rats. Baseline brain stimulation reward thresholds did not differ between the two groups of rats. Additionally, brain stimulation reward thresholds for the two groups were not differentially affected by d-amp. The above results suggest that HR and LR can be further differentiated upon exposure to a novel environment and in response to d-amp. This differentiation is primarily based on qualitative cohorts of their behavioral structure, but not on deviations in the reward processes as assessed by intracranial self-stimulation.

Animals↗
PubMed2004

Implication of spinal protein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain-like state in mice.

We previously demonstrated that spinal protein kinase C (PKC) is involved in the development of a neuropathic pain-like state induced by sciatic nerve ligation, and the morphine-induced rewarding effect is attenuated by sciatic nerve ligation in rodents. Here we first investigated whether sciatic nerve injury could change the activity of a conventional PKC (cPKC) and an atypical PKC isoform PKCzeta in the mouse spinal cord. The second experiment was to investigate whether direct inhibition of spinal PKC by intrathecal (i.t.) administration of a specific PKC inhibitor, 2-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-3-(1-methyl-1H-indole-3-yl)maleimide (RO-32-0432), could affect the rewarding effect induced by morphine following sciatic nerve ligation in mice. We found here that the activities of both cPKC and PKCzeta in the spinal cord were clearly increased following sciatic nerve ligation. Furthermore, i.t. administration of RO-32-0432 reversed a long-lasting pain-like syndrome as indicated by thermal hyperalgesia following sciatic nerve ligation in mice. These data provide direct evidence that activated cPKC and PKCzeta in the spinal cord may contribute to the development and maintenance of neuropathic pain. In the present study, we confirmed that the morphine-induced place preference was significantly suppressed by sciatic nerve ligation. It should be mentioned that i.t. pretreatment with RO-32-0432 significantly reversed the attenuation of morphine-induced rewarding effect following sciatic nerve ligation. These results suggest that activation of PKCs, including cPKC and PKCzeta, within the spinal cord is directly responsible for the attenuation of the morphine-induced rewarding effect under a neuropathic pain-like state following sciatic nerve ligation in mice.

Analgesics, Opioid↗
PubMed2005

Nucleus accumbens dopamine release is necessary and sufficient to promote the behavioral response to reward-predictive cues.

The nucleus accumbens is part of the neural circuit that controls reward-seeking in response to reward-predictive cues. Dopamine release in the accumbens is essential for the normal functioning of this circuit. Previous studies have shown that injection of dopamine receptor antagonists into the accumbens severely impairs an animal's ability to perform operant behaviors specified by predictive cues. Furthermore, excitations and inhibitions of accumbens neurons evoked by such cues are abolished by inactivation of the ventral tegmental area, the major dopaminergic input to the accumbens. These results indicate that dopamine is necessary to elicit neural activity in the accumbens that drives the behavioral response to cues. Here we show that accumbens dopamine release is causal to the rats' reward-seeking behavioral response by demonstrating that dopamine in this structure is both necessary and sufficient to promote the appropriate behavioral response to reward-predictive cues.

Animals↗
PubMed2006

Characterization of dopamine-dependent rewarding and locomotor stimulant effects of intravenously-administered methylphenidate in rats.

In general, psychostimulants are thought to exert rewarding and locomotor stimulating effects via increased dopamine transmission in the ventral striatum. However, little is known about the mechanisms underlying the effects of the stimulant drug methylphenidate. The present study examined the putative role of dopaminergic transmission in i.v. methylphenidate reward as measured by conditioned place preference. Rats were shown to exhibit conditioned place preference for i.v. methylphenidate (5 mg/kg, not 2 mg/kg). Administration of the dopamine receptor antagonist cis-flupenthixol (0.1-0.8 mg/kg i.p.), either during conditioning or on test day, dose-dependently attenuated the magnitude of the conditioned place preference. Finally, we examined the effects of bilateral 6-hydroxydopamine lesions of nucleus accumbens core, medial shell or anteromedial olfactory tubercle on the rewarding and locomotor stimulant effects of methylphenidate. Residual dopamine innervation, as assessed by radioligand binding to the dopamine transporter, revealed a significant association between core dopamine innervation and the locomotor stimulant effect of methylphenidate. However, neither core nor medial shell dopamine innervation was related to conditioned place preference magnitude. Instead, conditioned place preference magnitude was associated with dopamine innervation in the anteromedial olfactory tubercle. These results establish a role for dopaminergic transmission in both i.v. methylphenidate conditioned place preference and locomotor stimulation. As well, they suggest that different ventral striatal subregions mediate the rewarding (anteromedial olfactory tubercle) and locomotor stimulant (accumbens core) effects of methylphenidate.

Adrenergic Agents↗
PubMed2005

The role of the GABA(A) agonist muscimol on memory performance: reward contingencies determine the nature of the deficit.

A matching-to-position (MTP) paradigm was altered to influence the type of associations a rat would use to solve the task. Our main behavioral manipulation was the application of the differential outcomes procedure (DOP). The DOP involves correlating each to-be-remembered event with a distinct reward condition. This procedure results in the development of unique reward expectancies that enhance and guide choice behavior. Such distinct reward expectancies are not formed when either a common or random assignment of reward is used (a non-differential outcomes procedure [NOP]). Intracerebroventricular infusions of the amnestic agent muscimol (GABA(A) agonist) or aCSF were delivered to male rats trained on a delayed MTP task that implemented either the DOP or the NOP. Muscimol impaired performance in a dose dependent fashion in both groups--but the nature of the deficit differed as a function of reinforcement contingencies. Rats trained with the DOP displayed a non-mnemonic delay-independent impairment: performance at all delay intervals was disrupted. In contrast, NOP-trained rats displayed a delay-dependent impairment demonstrating that muscimol can also have memory-disrupting effects. The difference in pattern of impairment appears to be a function of the associations formed during training and the type of cognitive strategies involved in maintaining behavior on a conditional delayed discrimination task when reinforcement contingencies are varied. Thus, these results demonstrate that increasing GABA(A) receptor activation impairs a range of associative and memory functions.

Animals↗
PubMed2006

Adolescent reward system perseveration due to nicotine: studies with methylphenidate.

Previous data suggests adolescent nicotine exposure permanently disrupts reward systems. Behavioral pharmacological methods were used to assess the effects of adolescent nicotine exposure on methylphenidate (MPD) sensitivity and reward from adolescence to adulthood. For experiment one, testing was performed on adult mice exposed to nicotine (0.3 and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during adolescence (PND 25-57). After a 28-day drug-free, time-off period, the locomotor effects (30 min, 30 cm traveled) of MPD (5, 10, 20, and 40 mg/kg, IP) were measured. Thereafter, mice underwent condition-place-preference testing (CPP). MPD (20 mg/kg) was paired with the subject's non-preferred side and saline with the preferred side. Conditioning sessions were conducted for 8 days with a drug-free post-test on the day following the final conditioning session. A second experiment was conducted to determine if adolescent mice respond differently to MPD compared to adult mice. The study compared adolescent mice (PND 25-46) to adult mice (PND 77-98) using identical MPD testing procedures as in experiment one. Adult subjects exposed to nicotine during adolescence behaved remarkably similar to adolescent subjects receiving only MPD. Both nicotine exposed subjects and naïve adolescents exhibited increased response to MPD's motor activating effects and a decreased response to MPD's rewarding effects. Taken together it appears that adolescent nicotine exposure retards the development of reward systems, thus, maintaining an adolescent state indefinitely, which could result in increased vulnerability to substance abuse problems throughout adulthood.

Age Factors↗
PubMed2004

Effects of morphine on brain-stimulation reward thresholds in young and aged rats.

Mesolimbic opioid systems are altered with aging; however, the effects of these changes on the rewarding actions of opioids have not been examined. The present experiment assessed differences in the responsiveness of brain reward pathways in young and aged rats to the effects of morphine using the brain-stimulation reward (BSR) model. Aged (24 months) and young (5 months) male F344/BNF1 rats were stereotaxically implanted with a bipolar stainless steel electrode into the lateral hypothalamic (LH) region of the medial forebrain bundle. Thresholds were determined using the rate-independent psychophysical method. Each animal was tested after the administration of saline or morphine at 0.5, 1, 2.5, 5 and 10 mg/kg doses. A significant difference in the mean baseline threshold between aged (99.8+/-6 microA) and young rats (149.1+/-14 microA) was observed. Although in both groups morphine lowered the BSR threshold, there were no significant differences between the groups except at the 10-mg/kg dose, the difference did approach significance. This study indicates that there are baseline differences in the rewarding threshold in the two groups, that morphine lowers the threshold in young and aged animals and that the hedonic effects produced by morphine, for the most, part remain preserved in aged animals.

Aging↗
PubMed2005

Rewarding properties of the stereoisomers of 4-methylaminorex: involvement of the dopamine system.

4-Methylaminorex is a potential psychostimulant drug of abuse that exists as four stereoisomers: cis-4R,5S, cis-4S,5R, trans-4S,5S, and trans-4R,5R. The racemic mixture of the cis-isomers has been encountered in illicit samples, but previous animal studies suggest that also the trans-isomers could have similar stimulant-like properties. We tested whether the stereoisomers possess rewarding properties and compared their potency using the conditioned place preference method in rats. Furthermore, the involvement of the brain dopaminergic system in the 4-methylaminorex reward was tested with the dopamine D1- and D2-receptor antagonists SCH 23390 and raclopride administered systemically, or with the neurotoxin 6-hydroxydopamine injected into the nucleus accumbens. All the four isomers induced place preference, with no apparent differences in their potency. SCH 23990 and raclopride attenuated 4-methylaminorex-induced increase in place preference, and 6-hydroxydopamine also tended to be efficacious. These findings indicate that all the four stereoisomers of 4-methylaminorex possess rewarding properties and thus abuse potential; the trans-isomers are at least as potent as the cis-isomers. Furthermore, the brain dopaminergic system appears to be involved in the 4-methylaminorex-reward.

Analysis of Variance↗
PubMed2004

The relationship between food reward and satiation revisited.

The postingestive satiating action of food is often viewed as producing a positive affective state that rewards eating. However, in an early test of this idea, Van Vort and Smith [Physiol. Behav. 30 (1983) 279] reported that rats did not learn to prefer a food that was "real-fed" and satiating over a food that was "sham-fed" and not satiating. Subsequent investigators obtained similar findings with concentrated nutrient sources. With dilute nutrient sources, however, rats learned to prefer the real-fed to the sham-fed food. These and other findings demonstrate that nutrients have rewarding postingestive effects that enhance food preferences via a conditioning process. These reward effects appear separate from the satiating actions of nutrients, which may actually reduce food reward. Food intake and preference are controlled by a complex interaction of positive and negative signals generated by nutrients in the mouth and at postingestive sites.

Animals↗
PubMed2005

Rapid learning and flexible memory in "habit" tasks in rats trained with brain stimulation reward.

Two groups of rats, one rewarded with sweetened food and the other rewarded with medial forebrain bundle (MFB) stimulation, were trained to home in on and dig for a buried object coated with a target odor. After each group had 15 training trials, MFB rats searched with greater accuracy and speed than food-rewarded rats. MFB rats were subsequently tested (1) after 6 weeks with no additional practice; (2) with food or non-food distractor odors, and (3) with major spatial alterations to the search environment, and in all cases searched with the same high accuracy, short search time, and low level of distractibility as in baseline. These results suggest that the high motivation provided by MFB reward engenders rapidly formed, long-lasting, and surprisingly flexibly deployable "habit" memories.

Animals↗
PubMed2006

Gustatory reward and the nucleus accumbens.

The concept of reward is central to psychology, but remains a cipher for neuroscience. Considerable evidence implicates dopamine in the process of reward and much of the data derives from the nucleus accumbens. Gustatory stimuli are widely used for animal studies of reward, but the connections between the taste and reward systems are unknown. In a series of experiments, our laboratory has addressed this issue using functional neurochemistry and neuroanatomy. First, using microdialysis probes, we demonstrated that sapid sucrose releases dopamine in the nucleus accumbens. The effect is dependent on oral stimulation and concentration. We subsequently determined that this response was independent of the thalamocortical gustatory system, but substantially blunted by damage to the parabrachial limbic taste projection. Further experiments using c-fos histochemistry confirmed that the limbic pathway was the prime carrier for the gustatory afferent activity that drives accumbens dopamine release.

Afferent Pathways↗
PubMed2005

Reviewing the effort-reward imbalance model: drawing up the balance of 45 empirical studies.

The present paper provides a review of 45 studies on the Effort-Reward Imbalance (ERI) Model published from 1986 to 2003 (inclusive). In 1986, the ERI Model was introduced by Siegrist et al. (Biological and Psychological Factors in Cardiovascular Disease, Springer, Berlin, 1986, pp. 104-126; Social Science & Medicine 22 (1986) 247). The central tenet of the ERI Model is that an imbalance between (high) efforts and (low) rewards leads to (sustained) strain reactions. Besides efforts and rewards, overcommitment (i.e., a personality characteristic) is a crucial aspect of the model. Essentially, the ERI Model contains three main assumptions, which could be labeled as (1) the extrinsic ERI hypothesis: high efforts in combination with low rewards increase the risk of poor health, (2) the intrinsic overcommitment hypothesis: a high level of overcommitment may increase the risk of poor health, and (3) the interaction hypothesis: employees reporting an extrinsic ERI and a high level of overcommitment have an even higher risk of poor health. The review showed that the extrinsic ERI hypothesis has gained considerable empirical support. Results for overcommitment remain inconsistent and the moderating effect of overcommitment on the relation between ERI and employee health has been scarcely examined. Based on these review results suggestions for future research are proposed.

Cardiovascular Diseases↗
PubMed2006

Cultural coevolution of norm adoption and enforcement when punishers are rewarded or non-punishers are punished.

A number of studies have shown that social norms can be maintained at a high frequency when norm-violators are punished. However, there remains the problem of how norm-adopters and punishers coevolve within a single group. We develop a recursive system to examine the coevolution of norm-adopters and punishers where the viability of punishers is enhanced by one of two "metanorms": (1) Norm-observers reward punishers for punishing norm-violators (Reward Model); (2) Punishers punish non-punishers (Punishment Model). Both models generate a bistable system and each is characterized in phenotype frequency space by a distinct region of attraction to the equilibrium consisting of only norm-adopting punishers. Using a Monte Carlo simulation, we find that cultural drift may allow norm-adopters and punishers to coevolve from invasion into this region of attraction, resulting in their fixation. This coevolution typically occurs across a wider range of conditions under the reward- than the punishment-based metanorm. We also show that, under appropriate conditions, a large negative statistical association between the two traits may evolve only under the Reward Model. Furthermore, for each metanorm, a population of norm-adopters who always observe the norm can be locally stable over a continuum of punishment frequencies.

Cultural Evolution↗
PubMed2001

Disordered eating behaviors and reward sensitivity.

This research evaluated the extent to which reward sensitivity demonstrated associations with binge and purge behavior frequency. A verbal operant conditioning task designed to assess conditionability to reward cues was administered to a sample of 34 women who exhibited disordered eating patterns for at least I month prior to study participation. Reward sensitivity significantly correlated with the average weekly frequency of purge (r = 0.44) but not binge behaviors. These findings suggest that reward sensitivity has some associations with aspects of disordered eating and therefore may have relevance for theories on the maintenance of some forms of eating disorder-related behavior.

Adolescent↗
PubMed1997

Reward dependence is positively related to urinary monoamines in normal men.

According to Cloninger, three major personality dimensions, novelty seeking, harm avoidance, and reward dependence, are dependent on central monoaminergic systems. This study examined the relationship between the urinary levels of different monoamines and the above personality dimensions. Fifty normal men answered the Tridimensional Personality Questionnaire (TPQ); their levels of dopamine, norepinephrine, epinephrine, normetanephrine, metanephrine, 3-methoxy-4-hydroxyphenylglycol, vanilmandelic acid, homovanilic acid, and serotonin metabolite 5-hydroxyindolacetic acid were measured in urine on two consecutive nights. Significant and positive correlations were found between reward dependence, 3-methoxy-4-hydroxyphenylglycol, and epinephrine (r = .50 and r = .51, respectively). Monoamine levels explained 44% of the variance of reward dependence. Cluster analysis identified three groups of subjects presenting specific patterns of monoamine excretion. The TPQ scores could discriminate among subjects belonging to these clusters. These results point out a narrow relationship between urinary monoamine excretion and the basic personality dimension of reward dependence.

Adult↗
PubMed2000

CRF and urocortin decreased brain stimulation reward in the rat: reversal by a CRF receptor antagonist.

The present studies were designed to investigate the effects of corticotropin-releasing factor (CRF) receptor activation and antagonism on intracranial self-stimulation (ICSS) reward using a discrete-trial current-intensity threshold procedure. Bipolar electrodes were implanted in the lateral hypothalamus, and cannula guides were implanted above the lateral ventricle of male Wistar rats. Dose-effect functions were established for the effects on ICSS of the competitive CRF receptor agonist h/rCRF (0-5.0 microg, i.c.v. ), the CRF receptor agonist urocortin (0-5.0 microg, i.c.v.), and the CRF receptor antagonist [D-Phe(12), Nle(21,38), C(alpha) MeLeu(37)] h/rCRF(12-41) (0-5.0 microg, i.c.v.). Administration of h/rCRF or urocortin dose-dependently elevated ICSS thresholds without altering performance measures (latencies to respond to stimulation, extra and time-out responses). CRF was more potent than urocortin in terms of threshold dose-effects on ICSS thresholds compared to vehicle. Despite these apparent potency differences, percent effect sizes on ICSS thresholds were comparable at the highest doses of both peptides. In contrast to the significant threshold elevation effects of CRF and urocortin, the competitive CRF antagonist D-Phe CRF(12-41) had no effect on ICSS thresholds or performance measures. To determine the neuropharmacological specificity of the effect of CRF on brain stimulation reward, D-Phe CRF(12-41) was used to antagonize CRF-induced threshold elevations. Pretreatment with either the 5.0- or 10.0-microg doses of D-Phe CRF(12-41) effectively blocked CRF-induced reward threshold elevations (3.0 microg) without affecting other ICSS performance measures. These results indicate that CRF neurotransmission can modulate ICSS reward processes.

Animals↗
PubMed2000

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. 5 and 1.0 microl of 4% lidocaine produced immediate, substantial upward shifts in the frequency required to maintain half-maximal self-stimulation response rates whereas injecting comparable volumes of saline did not. Bilateral inactivation was particularly effective, especially at medium and high stimulation currents, although unilateral inactivation ipsilateral to the stimulation site was also effective. Contralateral inactivation alone did not substantially change the stimulation's reward value, although contralateral inactivation appeared to contribute to the effectiveness of bilateral inactivation. The frequency required to maintain half-maximal responding returned to baseline levels by 15-20 min after lidocaine infusion. In seven rats whose infusion sites were not in the RRF, lidocaine inactivation did not consistently degrade the stimulation's reward value. These results indicate that some neural elements located in the RRF contribute to the rewarding effect of MFB stimulation. Possible roles for these elements in the anatomical substrate for MFB self-stimulation are discussed.

Anesthetics, Local↗