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Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

Antipsychotic Agents↗

A double-blind placebo controlled experimental study of nicotine: I--effects on incentive motivation.

RATIONALE: Brain reward pathways implicated in addiction appear to be less reactive in regular drug users; behavioural manifestations may include decreased sensitivity to natural reinforcers. OBJECTIVES: This study aimed to replicate earlier findings of abstinence-associated incentive motivation deficits in smokers and to determine whether these can be reversed with nicotine in the form of lozenge. METHODS: One hundred forty-five smokers were each tested twice, once after receiving nicotine, and once after receiving placebo lozenge in counterbalanced order. Participants completed various tests of incentive motivational functioning: a measure of subjective enjoyment, the Snaith-Hamilton pleasure scale (SHAPS); a simple card sorting task, the card arranging reward responsivity objective test (CARROT) with and without financial incentive; the modified emotional Stroop test; a cue-reactivity task; and a novel reaction time task to explore effects of signals of reward, the incentive motivational enhancement of response speed task. RESULTS: Compared with performance during abstinence (placebo condition), nicotine was associated with: higher self-reported pleasure expectations on the SHAPS; enhanced responsiveness to financial reward on the CARROT in smokers who smoked 15 or more cigarettes a day; and greater interference from appetitive words on the Stroop task. CONCLUSIONS: These results are generally consistent with contemporary neurobiological theories of addiction and suggest that short-term smoking abstinence is associated with impaired reward motivation which can be reversed with nicotine.

Adult↗

Results of a year-long incentives-based worksite smoking-cessation program.

This study evaluated the impact of a year-long incentives-based worksite smoking-cessation program. Nineteen moderate-sized worksites, employing a total of approximately 1100 smokers, were randomized to Incentive or No Incentive conditions. All identified smokers in the worksite were considered as subjects, whether or not they participated in the intervention. Analyses were conducted at both the worksite and individual level, and using both self-reported and biochemically validated cessation as endpoints. The incentive program did not significantly improve cessation rates at either the 1-year or 2-year follow-up assessments. We conclude that more broadly focused interventions that also address worksite smoking policies, skills training, and cessation resources, or programs that target additional risk factors are needed to substantially enhance quit rates.

Academies and Institutes↗

Cost-effectiveness of prize-based incentives for stimulant abusers in outpatient psychosocial treatment programs.

OBJECTIVE: To evaluate the cost-effectiveness of a prize-based intervention as an addition to usual care for stimulant abusers. METHODS: This cost-effectiveness analysis is based on a randomized clinical trial implemented within the National Drug Abuse Treatment Clinical Trials Network. The trial was conducted at eight community-based outpatient psychosocial drug abuse treatment clinics. Four hundred and fifteen stimulant abusers were assigned to usual care (N=206) or usual care plus abstinence-based incentives (N=209) for 12 weeks. Participants randomized to the incentive condition earned the chance to draw for prizes for submitting substance negative samples; the number of draws earned increased with continuous abstinence time. Incremental cost-effectiveness ratios were estimated to compare prize-based incentives relative to usual care. The primary patient outcome was longest duration of confirmed stimulant abstinence (LDA). Unit costs were obtained via surveys administered at the eight participating clinics. Resource utilizations and patient outcomes were obtained from the clinical trial. Acceptability curves are presented to illustrate the uncertainty due to the sample and to provide policy relevant information. RESULTS: The incremental cost to lengthen the LDA by 1 week was 258 US dollars (95% confidence interval, 191-401 US dollars). Sensitivity analyses on several key parameters show that this value ranges from 163 to 269 US dollars. CONCLUSIONS: Compared with the usual care group, the incentive group had significantly longer LDAs and significantly higher costs.

Cost-Benefit Analysis↗

Microanalysis of the relationship between goal self-efficacy and cardiovascular reactivity. A test for the moderating role of incentive value and the mediating role of anxiety.

Eighty-three subjects were asked to solve a series of 15 mathematical problems after having been randomly assigned to an easy (5 problems) or to a difficult (9 problems) performance challenge. In addition to this, in order to create a sense of threat, subjects were told that a loud noise would be contingent upon failing to attain the performance challenge. Goal self-efficacy was computed from calculating the difference between self-efficacy level and the performance challenge. Intrinsic incentive value was derived from a six-item scale measuring the intensity of negative affects expected by the subject to be contingent upon a hypothetical failure to attain the goal. Systolic and diastolic blood pressure, and heart rate were collected during both the task performance and a prior rest phase. Anxiety-state was measured during the task performance as well. Statistical analyses revealed that interaction of goal self-efficacy and intrinsic incentive value partially predicted systolic blood pressure and heart rate reactivity. A main effect of self-efficacy was found on diastolic blood pressure. Overall, data best fitted to non-linear, quadratic functions in which either very low or very high self-efficacy, jointly with high incentive value, led to an enhanced cardiovascular reactivity. These findings are partially consistent with those previously obtained, and point to a complex model in which self-efficacy exerts specific effects on each cardiovascular parameter, usually in a non-monotonical way. Again, incentive value appeared as a moderator, but anxiety-state did not appear as a mediator of the relationship between goal self-efficacy and cardiovascular reactivity.

Adult↗

Prepayment was superior to postpayment cash incentives in a randomized postal survey among physicians.

OBJECTIVE: Improving response rates, particularly among physicians, is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research. We conducted a randomized trial to examine the impact of prepayment vs. postpayment incentives on response rates. STUDY DESIGN AND SETTING: Self-completion postal questionnaires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong. These physicians were randomly allocated to receive a HK dollar 20 cash prepayment incentive that accompanied the survey (n=474) or a postpayment reward of the same amount on receipt of the completed questionnaire (n=475). RESULTS: The final prepayment response rate was 82.9%, compared with 72.5% in the postpayment arm (P < .001). Of the eight alternative incentive and follow-up strategies evaluated, three lie on the efficiency frontier (i.e., not dominated), including postpayment with three mailings at HK dollar 42.7, prepayment with three mailings at HK dollar 66.5 and prepayment with three mailings and telephone follow-up at HK dollar 112.1 per responder recruited (US dollar 1=HK dollar 7.8). CONCLUSION: The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians. Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and settings.

Attitude of Health Personnel↗

Use of a low-cost incentive intervention to improve counseling attendance among methadone-maintained patients.

Despite the importance of counseling in methadone maintenance treatment, many patients do not take advantage of these services. Incentives for attending group counseling were offered to methadone-maintained patients during an orientation phase of treatment or during required attendance at a relapse group later in treatment. Upon attending each counseling session, patients could draw for prizes under an escalating draw system with a 50% probability that draws would result in a prize. Incentives included small (1dollar), moderate (5 dollars), and large (20 dollars) prizes, with chances of winning inversely related to prize costs, and a maximum possible total of 160 dollars per patient. It was anticipated that this policy would provide a relatively low-cost approach to improving counseling attendance in our methadone clinic. The incentive policy significantly increased the percent of counseling sessions attended (52% vs. 76%) and promoted periods of continuous attendance. These data further support the effectiveness of low-cost incentive programs in enhancing counseling attendance among methadone patients.

Adult↗

If 'atypical' neuroleptics did not exist, it wouldn't be necessary to invent them: perverse incentives in drug development, research, marketing and clinical practice.

Perverse incentives in drug development, research, marketing and clinical usage can be illustrated by considering the example of the so-called 'atypical' neuroleptics which have grown to become a standard - indeed expanding - part of psychiatric practice despite their probable inferiority to older sedative agents. There is now ample evidence to suggest that neuroleptics (aka. anti-psychotics and major tranquillizers) are dangerous drugs, and patients' exposure to them should be minimized wherever possible. This clinical imperative applies whether neuroleptics are of the traditional type or atypical variety, albeit for different reasons since the traditional agents are neurotoxic, while atypicals are mainly metabolic poisons. Usage of traditional neuroleptics seems indeed to be declining progressively, but the opposite seems to be happening for 'atypicals', and new indications for these drugs are being promoted. Yet the atypical neuroleptics are a category of pharmaceuticals which are close to being un-necessary since there are safer, cheaper and pleasanter substitutes, such as benzodiazepines and the sedative antihistamines (e.g. promethazine). If 'atypical' neuroleptics did not exist, it would not be necessary to invent them. Analysis of how such expensive, dangerous and inferior drugs as the 'atypicals' have nevertheless come to dominate clinical practice casts light on the perverse incentives which now motivate the pharmaceutical industry in an era of massive state regulation. The lack of positive incentives to deploy off-patent drugs is longstanding, but there is a new disincentive in the widespread but erroneous belief that only randomized controlled trials (RCTs) can provide valid 'evidence' of effectiveness. Consequently, those who control RCTs now control clinical practice. It sometimes makes commercial sense to develop and market new drugs that are inferior to existing agents, since new drugs are patent-protected and can be promoted on the back of a mass of new RCTs funded and 'owned' by the pharmaceutical corporations. The current regulatory and patenting situation, therefore, requires major reform if drug efficacy and patient safety are to become higher priorities. Given that psychiatric practice is apparently 'locked-in' to prescribing atypicals, and if (as seems likely) most informed individuals would wish to avoid neuroleptics for themselves and their loved-ones except as a last resort; then in the short-term it may be wise for patients and their families to explore the possibilities of increased self-management of psychiatric problems using over-the-counter drugs, such as the sedative antihistamines. In the long-term, there need to be legal reforms to change the regulatory and commercial framework of incentives relating to drug development. These might include new forms of short-term re-patenting of old drugs.

Antipsychotic Agents↗

Sexual-incentive motivation and paced sexual behavior in female rats after treatment with drugs modifying dopaminergic neurotransmission.

The effects of the dopamine receptor agonist apomorphine, the dopamine releaser amphetamine, and the dopamine receptor antagonist cis(Z)-flupenthixol on sexual-incentive motivation and on paced-mating behavior were studied in female rats. Apomorphine, in the doses of 0.125 and 0.5 mg/kg, showed a tendency to reduce incentive motivation. Ambulatory activity was inhibited, evidenced both by diminished distance moved and reduced velocity of movement. Amphetamine (0.25 and 1 mg/kg) and flupenthixol (0.25 and 0.5 mg/kg) failed to modify incentive motivation while stimulating and reducing ambulatory activity, respectively. In the mating test, apomorphine enhanced the latency to enter the male's half and reduced the number of proceptive behaviors. However, these effects were associated with the appearance of stereotyped sniffing. Amphetamine increased the propensity to escape from the male after a mount without having other effects. Flupenthixol augmented the duration of the lordosis posture. Neither amphetamine nor flupenthixol affected sniffing. These data show that facilitated dopaminergic neurotransmission stimulates neither paced female sexual behavior nor sexual-incentive motivation. Dopamine receptor blockade has slight consequences. It is concluded that dopamine is not a transmitter of major importance for unconditioned female sexual motivation and behavior.

Amphetamine↗

Pharmacogenomics, genetic tests, and patent-based incentives.

Pharmacogenomics promises to revolutionize medicine by using genetic information to guide drug therapy. Genetic tests should help doctors improve drug safety and efficacy by better matching patients and drugs. This chapter evaluates the effectiveness of patent-based incentives to create genetic tests, and considers the optimal mix of public and private sector pharmacogenomic research and development (R&D). Drug patent owners have a strong incentive to develop genetic tests that predict adverse drug reactions and allow them to market drugs that otherwise would be shelved. Incentives are also strong for genetic tests that are created as part of the drug development process. Incentives tend to be weaker for genetic tests that are used in conjunction with existing drugs. Drug patent owners might gain or lose profit from the introduction of genetic tests into existing drug markets. Profits may fall because of lost sales, or profits may rise because drugs are more valuable to appropriate patients, and because drugs become more differentiated. Public sector R&D should target genetic tests that are likely to be underprovided by the private sector because private returns are low relative to social returns, or private costs are high relative to social costs. Private returns are relatively low when the rate of adoption of a genetic test is apt to be low, when test results increase consumer heterogeneity and consumer bargaining power, and when a test reveals information relevant to the use of more than one drug. Private costs are relatively high when test innovators need to obtain costly patent and trade secret licenses.

Ethics, Medical↗

Dopamine D1-like receptors and reward-related incentive learning.

There now is general agreement that dopaminergic neurons projecting from ventral mesencephalic nuclei to forebrain targets play a critical role in reward-related incentive learning. Many recent experiments evaluate the role of dopamine (DA) receptor subtypes in various paradigms involving this type of learning. The first part of this paper reviews evidence from these studies that use antagonists or agonists relatively specific for D1- or D2-like receptors in operant paradigms with food, brain stimulation, self-administered stimulant or conditioned rewards or place conditioning. The focus is on studies that directly compare agents acting at the two DA receptor families, especially those studies where the agents produce differential actions. Results support the conclusion that D1-like receptors play a more critical role in reward-related learning than D2-like receptors. D1-like receptors initiate a cascade of intracellular events including cyclic adenosine monophosphate (cAMP) formation and activation of cAMP-dependent protein kinase (PKA). The final section of this paper reviews evidence from a wide range of neuroscience experiments that implicates the cAMP/PKA pathway in learning in general and in reward-related incentive learning in particular. We conclude that the molecular mechanism underlying DA-mediated incentive learning may involve DA release in association with reward, stimulation of D1-like receptors, activation of the cAMP/PKA cascade and additional intracellular events leading to modification of cortico-striatal glutamatergic synapses activated by stimuli encountered in close temporal contiguity with reward. Thus, when reward-related incentive learning takes place, it may be the action of DA acting at D1-like receptors that leads to plastic changes in the striatum that form the substrate of that learning.

Animals↗

What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is 'no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the 'taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary for 'wanting' incentives, but not for 'liking' them or for learning new 'likes' and 'dislikes'.

Animals↗

Incentives and health policy: primary and secondary care in the British National Health Service.

This paper argues that issues concerning incentives and motivation are crucial to recent reforms to the British National Health Service. It examines how the incentive structure of General Practitioners with respect to the interface between primary and secondary care changed with the introduction of GP fundholding, and how it might change further with the new Primary Care Groups. It concludes that the effectiveness of the internal incentive structure of the new groups will depend on the location of power within the PCGs, and that the external incentives involving the possibility of heavy central monitoring may affect the behaviour and motivation of GPs in potentially harmful ways.

Family Practice↗

The role of perceived control in physiological reactivity: self-efficacy and incentive value as regulators of cardiovascular adjustment.

The aim of this study was to verify the influence of self-efficacy and incentive value on cardiovascular reactivity. Ninety-six subjects were randomly assigned to four experimental groups in each of which the self-efficacy (high or low) and incentive value (high or low) were modified in relation to a mental arithmetic task. Subjects were led to believe that failure in this behaviour would result in the appearance of an aversive stimulus. Heart rate, systolic and diastolic blood pressure, pulse pressure and skin temperature were all recorded throughout task performance, and at two given moments prior to the task, in order to establish baseline values. Subjects with high self-efficacy experienced a smaller increase in heart rate and systolic pressure, a greater increase in diastolic pressure, greater reduction in skin temperature and a reduction in pulse pressure during task performance. The effects were moderated by the incentive value in such a way that the effects of self-efficacy on cardiovascular reactivity were stronger when the consequences of task failure were perceived as highly relevant (high incentive value).

Adolescent↗

The effectiveness of incentives in enhancing treatment attendance and drug abstinence in methadone-maintained pregnant women.

This study examined the effectiveness of short-term contingency management for eliminating cocaine use and increasing full day treatment attendance with pregnant methadone-maintained women randomly assigned to either an escalating voucher incentive schedule (n=44) or non-incentive (n=36) conditions. Full day treatment attendance and urine toxicology for cocaine and heroin were assessed and consequated for 14 days. The escalating voucher incentive schedule significantly increased full day treatment attendance and drug abstinence compared to the non-incentive schedule. These results suggest that reinforcing the co-occurrence of two required behaviors (treatment attendance and abstinence from illicit drug use) is effective, and may be an important adjunct to methadone pharmacotherapy for treating pregnant drug dependent women.

Adult↗

Attendance incentives for outpatient treatment: effects in methadone- and nonmethadone-maintained pregnant drug dependent women.

The effectiveness of behavioral incentives for improving treatment participation and retention in samples of methadone-maintained (n = 66) and nonmethadone-maintained (n = 76) pregnant drug dependent women was examined. Subjects were randomly assigned to receive $0 (standard care) and $1, $5, or $10/day for attending at least 4 h of interdisciplinary treatment programming during the first 7 consecutive days after transfer from residential to outpatient care, with payment dispensed in the form of gift certificates. Methadone-maintained women attended nearly twice as many full treatment days as those not receiving methadone (5.2 vs 2.8 days; P < 0.001) and were retained in treatment significantly longer (86.4 vs 28.9% active in treatment at 30 days). There was no main effect of incentives and no effect on attendance in methadone patients. However, nonmethadone patients offered higher magnitude incentives ($5/$10) attended 3.3 days out of 7 on average, compared to 2.3 days for those offered $0 or $1 per day (t = 1.73; P < 0.05). The study confirmed that methadone maintenance is a powerful therapeutic adjunct which is associated with significantly better treatment retention and participation in ancillary programming than is abstinence-based treatment. It was also found that modest financial incentives can facilitate treatment participation for abstinence-based patients. However, more potent interventions would be needed to match the effectiveness of methadone in this regard.

Adolescent↗

Incentives and barriers to retinopathy screening among African-Americans with diabetes.

Diabetes-related ophthalmic complications are the leading cause of newly diagnosed blindness among adults. These eye complications are often asymptomatic in the early stages, yet the majority of diabetes patients are not screened yearly. To develop a health promotion intervention to increase the rate of screening for diabetic retinopathy by dilated fundus exam (DFE), we assessed the knowledge and health beliefs related to preventing diabetic eye complications among a sample of African-Americans with diabetes. The study design was cross-sectional, using a telephone interview to collect data. From a random sample of 104 African-Americans with diabetes, 67 (64%) were completed: 54 women; mean age of 58 years. The telephone interview schedule contained items grouped into subscales for Perceived Incentives, Perceived Barriers to getting a DFE, Causes of Eye Problems, Risk of Eye Problems, and Effective Treatments for Eye Problems. Descriptive statistics were used to analyze the quantitative data. Transcribed qualitative responses to the open-ended questions were analyzed for themes. The incentives "having eye problems" and "doctor said it was important to go" each had 91% responding it was an incentive to go for a DFE. Only about one-third agreed that any particular item was a barrier to receiving a DFE (e.g., economic factors). In the subscale for Risk of Eye Problems, "retinopathy" had the lowest level of perceived risk (30%). Only 21% of the sample reported there were effective treatments for retinopathy. Eighty-seven percent reported the faulty belief that "diabetic eye problems have symptoms." Only 36% of the sample said they had heard of retinopathy and of those, only 8% could describe it correctly. Among general response themes were: fear, spirituality (faith and hope), priorities, economic or logistical factors, and external/internal motivation. Perceived incentives for receiving a DFE were acknowledged at far greater rates than perceived barriers. Having a yearly DFE in the absence of symptoms must be emphasized in health promotion materials. There are effective, early treatments for diabetic eye problems, and this information should be used to counter the fear of a dreaded diagnosis with the hope of treatment and cure. Ways of coping with fear of having the exam should be included in health education. DFEs must become a routine yearly exam and not just a reaction to recognized problems. Health education must address the specific needs of high-risk minority populations.

Adult↗

Money as tool, money as drug: the biological psychology of a strong incentive.

Why are people interested in money? Specifically, what could be the biological basis for the extraordinary incentive and reinforcing power of money, which seems to be unique to the human species? We identify two ways in which a commodity which is of no biological significance in itself can become a strong motivator. The first is if it is used as a tool, and by a metaphorical extension this is often applied to money: it is used instrumentally, in order to obtain biologically relevant incentives. Second, substances can be strong motivators because they imitate the action of natural incentives but do not produce the fitness gains for which those incentives are instinctively sought. The classic examples of this process are psychoactive drugs, but we argue that the drug concept can also be extended metaphorically to provide an account of money motivation. From a review of theoretical and empirical literature about money, we conclude that (i) there are a number of phenomena that cannot be accounted for by a pure Tool Theory of money motivation; (ii) supplementing Tool Theory with a Drug Theory enables the anomalous phenomena to be explained; and (iii) the human instincts that, according to a Drug Theory, money parasitizes include trading (derived from reciprocal altruism) and object play.

Behavior, Addictive↗