Poor self-control, lack of inhibition, and impulsivity contribute to the propensity of adolescents to engage in risky or dangerous behaviors. Brain regions (e.g., prefrontal cortex) involved in impulse-control, reward-processing, and decision-making continue to develop during adolescence, raising the possibility that an immature brain contributes to dangerous behavior during adolescence. However, very few validated animal behavioral models are available for behavioral neuroscientists to explore the relationship between brain development and behavior. To that end, a valid model must be conducted in the relatively brief window of adolescence and not use manipulations that potentially compromise development. The present experiments used three operant arrangements to assess whether adolescent rats differ from adults in measures of learning, behavioral inhibition, and impulsivity, within the aforementioned time frame without substantial food restriction. In Experiment 1, separate squads of rats were trained to lever-press and then transitioned to two types of extinction. Relative to their baselines, adolescent rats responded more during extinction than adults, suggesting that they were less sensitive to the abolishment of the reinforcement contingency. Experiment 2 demonstrated similar age-related differences during exposure to a differential reinforcement of low rates schedule, a test of behavioral inhibition. Lastly, in Experiment 3, adolescent's responding decreased more slowly than adults during exposure to a resetting delay of reinforcement schedule, suggesting impaired self-control. Results from these experiments suggest that adolescents exhibit impaired learning, behavioral inhibition and self-control, and in concert with recent reports, provide researchers with three behavioral models to more fully explore neurobiology of risk-taking behavior in adolescence.

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Previous research has shown that corticostriatal N-methyl-D-aspartate receptor (NMDAR) activation is necessary for operant learning. NMDAR activation induces plasticity-related intracellular signaling processes leading to gene expression, which are hypothesized to be important steps in codifying the content of learning. Operant learning induces immediate early gene (IEG) expression in key corticostriatal structures, namely the dorsomedial striatum (DMS), the orbitofrontal (OFC), and anterior cingulate cortices (ACC). Both the ACC and OFC send glutamatergic projections to the DMS, which is a crucial site for operant behavior. However, the role of NMDAR activation in these corticostriatal regions in operant learning is unknown. To test this hypothesis, the NMDA antagonist AP-5 (1 microg/0.5 microl) or saline was bilaterally microinjected into the ACC, OFC, and DMS of food-deprived rats just prior to operant learning sessions. NMDAR antagonism in the ACC and DMS impaired the acquisition of lever pressing for sucrose pellets but had no effect on lever pressing once learned. NMDAR blockade in OFC did not significantly impair operant learning, suggesting that NMDAR activation in operant learning is site-specific. These data extend our understanding of the role of NMDA receptors in operant learning and behavior throughout an extended corticostriatal network.

AMPA-type glutamate receptors in the nucleus tractus solitarii (NTS) are necessary for the baroreceptor reflex, a primary mechanism for homeostatic regulation of blood pressure. Within NTS, the GluR1 subunit of the AMPA receptor is found primarily in dendritic spines. We previously showed that both GluR1 and dendritic spine density are increased in NTS of spontaneously hypertensive rats (SHRs). We hypothesize that both receptor and synaptic plasticity are induced by a sustained elevation in arterial pressure. To test the general nature of this hypothesis, we examined whether similar changes in GluR1 density are found in a renovascular model of hypertension, the DOCA-salt rat, and if these changes are preventable by normalizing blood pressure with hydralazine, a peripherally acting vasodilator. Using immunoperoxidase detection, GluR1 appears as small puncta at the light microscopic level, and is found in dendritic spines at the ultrastructural level. Following the development of hypertension, GluR1 spine and puncta counts were significantly greater in DOCA-salt rats than controls. Hydralazine treatment (4 -5 weeks) prevented the development of hypertension in DOCA-salt rats and reduced blood pressure of SHRs to normotensive levels. The density of GluR1 puncta in the NTS was significantly reduced by hydralazine treatment in the SHR model. These results show that hypertension alters dendritic spines containing AMPA-type glutamate receptors within NTS, suggesting that adjustments in GluR1 expression within NTS are part of the synaptic adaptations to the hypertensive state.

Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin®) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD.