RESUMEN
The annual "Roll Up the Rim to Win" contest at Tim Hortons restaurants provides customers the opportunity to win prizes. This study investigated win ratios, prize types and patterns of coffee consumption.
Asunto(s)
Bebidas , Café , Ingestión de Alimentos/fisiología , Distinciones y Premios , Canadá/epidemiología , Estudios de Seguimiento , Humanos , Prevalencia , Estudios Prospectivos , Valores de Referencia , Factores de Riesgo , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Caffeine is widely consumed throughout the world, but little is known about the mechanisms underlying its rewarding and aversive properties. We show that pharmacological antagonism of dopamine not only blocks conditioned place aversion to caffeine, but also reveals dopamine blockade-induced conditioned place preferences. These aversive effects are mediated by the dopamine D(2) receptor, as knockout mice showed conditioned place preferences in response to doses of caffeine that C57Bl/6 mice found aversive. Furthermore, these aversive responses appear to be centrally mediated, as a quaternary analog of caffeine failed to produce conditioned place aversion. Although the adenosine A(2A) receptor is important for caffeine's physiological effects, this receptor seems only to modulate the appetitive and aversive effects of caffeine. A(2A) receptor knockout mice showed stronger dopamine-dependent aversive responses to caffeine than did C57Bl/6 mice, which partially obscured the dopamine-independent and A(2A) receptor-independent preferences. Additionally, the A(1) receptor, alone or in combination with the A(2A) receptor, does not seem to be important for caffeine's rewarding or aversive effects. Finally, excitotoxic lesions of the tegmental pedunculopontine nucleus revealed that this brain region is not involved in dopamine blockade-induced caffeine reward. These data provide surprising new information on the mechanism of action of caffeine, indicating that adenosine receptors do not mediate caffeine's appetitive and aversive effects. We show that caffeine has an atypical reward mechanism, independent of the dopaminergic system and the tegmental pedunculopontine nucleus, and provide additional evidence in support of a role for the dopaminergic system in aversive learning.
Asunto(s)
Cafeína/farmacología , Condicionamiento Psicológico/efectos de los fármacos , Dopamina/metabolismo , Antagonistas de Receptores Purinérgicos P1/farmacología , Receptor de Adenosina A1/metabolismo , Receptor de Adenosina A2A/metabolismo , Receptores de Dopamina D2/metabolismo , Recompensa , Animales , Antagonistas de Dopamina/farmacología , Flupentixol/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora/efectos de los fármacos , Receptor de Adenosina A1/genética , Receptor de Adenosina A2A/genética , Receptores de Dopamina D2/genética , Tegmento Mesencefálico/anatomía & histologíaRESUMEN
Many organisms enter quiescence in response to adverse environmental factors. Here, we show that L1 stage C. elegans entered a quiescent state after 3hours exposure to diacetyl in which movement and growth stopped for hours to days after odorant removal. Entry into quiescence was dependent on neurons affected by the osm-3 mutation, and by AWA neurons. Conversely, AWB/AWC neurons, the guanylyl cyclase ODR-1, and the TRPV-channel subunit OCR-2 inhibited entry into L1 arrest. This quiescent behavior represents an alternative use of olfactory signaling pathways besides approach or avoidance, and is a novel model in which to characterize genes implicated in quiescence.
Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans , Diacetil/farmacología , Larva/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Factores de Edad , Animales , Relación Dosis-Respuesta a Droga , Actividad Motora/genética , Mutación , Odorantes , Células Receptoras Sensoriales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
The mesolimbic dopamine (DA) system is implicated in the processing of the positive reinforcing effect of all drugs of abuse, including nicotine. It has been suggested that the dopaminergic system is also involved in the aversive motivational response to drug withdrawal, particularly for opiates, however, the role for dopaminergic signaling in the processing of the negative motivational properties of nicotine withdrawal is largely unknown. We hypothesized that signaling at dopaminergic receptors mediates chronic nicotine withdrawal aversions and that dopaminergic signaling would differentially mediate acute vs dependent nicotine motivation. We report that nicotine-dependent rats and mice showed conditioned place aversions to an environment paired with abstinence from chronic nicotine that were blocked by the DA receptor antagonist alpha-flupenthixol (alpha-flu) and in DA D(2) receptor knockout mice. Conversely, alpha-flu pretreatment had no effect on preferences for an environment paired with abstinence from acute nicotine. Taken together, these results suggest that dopaminergic signaling is necessary for the opponent motivational response to nicotine in dependent, but not non-dependent, rodents. Further, signaling at the DA D(2) receptor is critical in mediating withdrawal aversions in nicotine-dependent animals. We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals.
Asunto(s)
Dopamina/metabolismo , Motivación/efectos de los fármacos , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Tabaquismo/fisiopatología , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal , Condicionamiento Operante/efectos de los fármacos , Modelos Animales de Enfermedad , Antagonistas de Dopamina/farmacología , Esquema de Medicación , Flupentixol/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Motivación/genética , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Receptores de Dopamina D2/deficiencia , Recompensa , Tabaquismo/psicologíaRESUMEN
The authors investigated the effect of the opioid antagonist naloxone on wheel-running behavior in Balb/c mice. Naloxone delayed the acquisition of wheel-running behavior, but did not reduce the expression of this behavior once acquired. Delayed acquisition was not likely a result of reduced locomotor activity, as naloxone-treated mice did not exhibit reduced wheel running after the behavior was acquired, and they performed normally on the rotarod test. However, naloxone-blocked conditioned place preference for a novel compartment paired previously with wheel running, suggesting that naloxone may delay wheel-running acquisition by blocking the rewarding or reinforcing effects of the behavior. These results suggest that the endogenous opioid system mediates the initial reinforcing effects of wheel running that are important in acquisition of the behavior.
Asunto(s)
Actividad Motora/fisiología , Péptidos Opioides/fisiología , Receptores Opioides/fisiología , Refuerzo en Psicología , Carrera/fisiología , Análisis de Varianza , Animales , Locomoción/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Actividad Motora/efectos de los fármacos , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Péptidos Opioides/antagonistas & inhibidores , Receptores Opioides/efectos de los fármacos , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.
Asunto(s)
Reacción de Prevención/fisiología , Dopamina/metabolismo , Nicotina/farmacología , Núcleo Accumbens/fisiología , Recompensa , Transmisión Sináptica/fisiología , Animales , Reacción de Prevención/efectos de los fármacos , Conducta de Elección/efectos de los fármacos , Condicionamiento Psicológico/efectos de los fármacos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Nicotina/administración & dosificación , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Oxidopamina/farmacología , Ratas , Ratas Long-Evans , Conducta Espacial/efectos de los fármacos , Gusto/fisiologíaRESUMEN
Considerable evidence suggests that psychostimulants can exert rewarding and locomotor-stimulating effects via increased dopamine transmission in the ventral striatum. However, the relative contributions of ventral striatal subregions to each of these effects have been little investigated. In the present study, we examined the contribution of different ventral striatal sites to the rewarding and locomotor-activating effects of cocaine. Initially, the effects of bilateral 6-hydroxydopamine lesions of the nucleus accumbens core or medial shell on cocaine-induced locomotor stimulation (0.5-1.5 mg/kg i.v. or 5-20 mg/kg i.p.) and conditioned place preference (0.5 mg/kg i.v. or 10 mg/kg i.p.) were examined. In a subsequent study, we investigated the effects of olfactory tubercle versus medial shell lesions on cocaine-conditioned place preference and locomotor activity (0.5 mg/kg i.v.). Dopaminergic lesion extent was quantified by radioligand binding to the dopamine transporter. Multiple linear regression was used to identify associations between behavioral effects and residual dopamine innervation in ventral striatal subregions. On this basis, the accumbens core was associated with the locomotor stimulant effects of i.v. and i.p. cocaine. In contrast, the medial shell was associated with the rewarding effect of i.v. cocaine, but not of i.p. cocaine. Finally, the olfactory tubercle was identified as an additional site contributing to conditioned place preference produced by i.v. cocaine. Overall, these findings provide additional evidence that the locomotor stimulant and rewarding effects of systemically administered psychomotor stimulant drugs are segregated within the ventral striatum.
Asunto(s)
Ganglios Basales/metabolismo , Estimulantes del Sistema Nervioso Central/toxicidad , Conducta de Elección/efectos de los fármacos , Cocaína/toxicidad , Actividad Motora/efectos de los fármacos , Refuerzo en Psicología , Animales , Ganglios Basales/efectos de los fármacos , Ganglios Basales/patología , Sitios de Unión , Mapeo Encefálico , Estimulantes del Sistema Nervioso Central/farmacocinética , Cocaína/farmacocinética , Masculino , Ratas , Ratas Long-EvansRESUMEN
Environmental cues associated with drug experiences appear to play a critical role in drug dependence. We have previously reported that dopamine-depleting lesions of the nucleus accumbens medial shell inhibit amphetamine-conditioned place preference. Here, we examined the effects of analogous lesions on amphetamine-conditioned locomotor activity. Bilateral core, but not medial shell, lesions attenuated unconditioned locomotion and abolished the conditioned locomotor response. Taken with our previous results, these findings confirm a role for accumbens core in amphetamine-induced locomotor activity and suggest that the role of medial shell DA transmission in conditioned place preference is related to reward processing rather than conditioning in general.
Asunto(s)
Anfetamina/farmacología , Condicionamiento Operante/efectos de los fármacos , Inhibidores de Captación de Dopamina/farmacología , Núcleo Accumbens/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Unión Competitiva/efectos de los fármacos , Cocaína/análogos & derivados , Cocaína/farmacocinética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Interacciones Farmacológicas , Actividad Motora/efectos de los fármacos , Núcleo Accumbens/anatomía & histología , Núcleo Accumbens/lesiones , Núcleo Accumbens/fisiología , Oxidopamina/toxicidad , Radiofármacos/farmacocinética , Ratas , Ratas Long-Evans , Simpaticolíticos/toxicidad , Tritio/farmacocinéticaRESUMEN
Convergent evidence suggests that amphetamine (AMPH) exerts its rewarding and locomotor stimulating effects via release of dopamine in the nucleus accumbens. However, there is no consensus as to the relative contributions of core and medial shell subregions to these effects. Moreover, the literature is based primarily on intracranial administration, which cannot fully mimic the drug distribution achieved by systemic administration. In the present study, the effects of bilateral 6-hydroxydopamine lesions of the accumbens core or medial shell on rewarding and locomotor stimulating effects of systemically administered amphetamine (0.75 mg/kg, i.p.) were examined in a conditioned place preference (CPP) procedure relying solely on tactile cues (floor texture). Residual dopamine innervation was quantified by [125I]-RTI-55 binding to the dopamine transporter. When lesions were performed before the conditioning phase, AMPH-induced locomotor stimulation and CPP magnitude were positively correlated with residual dopamine transporter binding in core and medial shell, respectively. Medial shell lesions did not affect morphine CPP, arguing that a sensory or mnemonic deficit was not responsible for the lesion-induced reduction in AMPH CPP. Medial shell lesions performed between the conditioning phase and the test day reduced the expression of amphetamine CPP. These results suggest that after systemic amphetamine administration, rewarding and locomotor stimulating effects of the drug are anatomically dissociated within the nucleus accumbens: the medial shell contributes to rewarding effects, whereas the core contributes to behavioral activation.