Consequences of Adolescent Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward.

Critical development of the prefrontal cortex occurs during adolescence, a period of increased independence marked by decision making that often includes engagement in risky behaviors, such as substance use. Consumption of alcohol during adolescence has been associated with increased impulsivity that persists across the lifespan, an effect which may be caused by long-term disruptions in cortical processing of rewards. To determine if alcohol consumption alters cortical encoding of rewards of different sizes and probabilities, we gave rats limited access to alcohol in gelatin during adolescence only. In adulthood, we recorded the electrophysiological activity of individual neurons of the orbitofrontal cortex while rats performed a risk task that varied the level of risk from day-to-day. Rats that had consumed higher levels of alcohol showed increased risk preference in the task compared with control and low alcohol-consuming rats. Patterns of neuronal responses were identified using principal component analysis. Of the multiple patterns observed, only one was modulated by adolescent alcohol consumption and showed strongest modulation after reward receipt. This subpopulation of neurons showed blunted firing rates following rewards in alcohol-consuming rats, suggesting a mechanism through which adolescent alcohol exposure may have lasting effects on reward processing in the context of decision making. The differences in OFC responses between high alcohol consumers and control animals not given access to alcohol support the idea that, regardless of potential variability in innate alcohol preferences, voluntary consumption of alcohol during adolescence biases choice patterns longitudinally through alterations in cortical function.

Anisomycin infusions in the parabrachial nucleus and taste neophobia.

To investigate whether de novo protein synthesis in the parabrachial nucleus (PBN) is required for recovery from taste neophobia, anisomycin (a protein synthesis inhibitor) was infused immediately after consumption of a novel saccharin solution (Experiment 1). Unexpectedly, this PBN treatment caused a reduction in saccharin intake. In addition, we found that the anisomycin-induced suppression of tastant intake was attenuated by prior intra-PBN infusions of lidocaine (Experiment 2). This pattern of results raises concerns about using anisomycin to investigate memory consolidation processes in the PBN. Thus, a different manipulation may be needed to examine the nature of the neuroplastic changes that occur in the PBN during taste memory formation.

Taste neophobia and palatability: the pleasure of drinking.

Taste neophobia is manifested behaviorally as lower intake of a novel, potentially dangerous tastant relative to the same tastant when it is perceived as safe and familiar. To further characterize this phenomenon, microstructural analysis of lick patterns was used to track the transition from novel to familiar for three tastants: saccharin, quinine and Polycose. The results revealed that in addition to an increase in the amount consumed (for saccharin and quinine but not Polycose), cluster size (an index of palatability) became larger as familiarity with the benign tastants increased. The current finding suggests that the pleasure of drinking increases as the novel, potentially dangerous tastant becomes accepted as safe.

Reduced palatability in drug-induced taste aversion: II. Aversive and rewarding unconditioned stimuli.

Drugs of abuse are known to reduce intake of a taste conditioned stimulus (conditional stimulus, CS), a behavioral response sometimes seen as paradoxical because the same drugs also serve as rewards in other behavioral procedures. In the present study we compared patterns of intake and palatability (assessed using microstructural analysis of licking) for a standard saccharin CS paired with the following: lithium chloride, morphine, amphetamine, or sucrose. We found that morphine and amphetamine, like lithium-induced illness, each suppressed CS intake and caused a reduction in saccharin palatability. Sucrose, a rewarding stimulus, did not reduce the palatability of the saccharin CS. We interpret these finds as evidence that drugs of abuse induce conditioned taste aversions.

Reduced palatability in drug-induced taste aversion: I. Variations in the initial value of the conditioned stimulus.

Like illness-inducing agents (e.g., lithium chloride), drugs of abuse also suppress intake of a taste solution. To explore the nature of this drug-induced intake reduction, in the current study three aqueous stimuli with different initial values served as the conditioned stimuli (CSs) that were paired with a standard dose of amphetamine in a voluntary intake procedure and lick patterns were analyzed. Consistent with earlier studies, amphetamine significantly reduced intake of all three CSs (quinine, sodium chloride, and orange odor). In contrast to studies that analyze orofacial responses, we found that lick cluster size was significantly lowered by amphetamine, indicating that the psychoactive drug induced a conditioned reduction in taste palatability.