Prefrontal Dopamine Receptors Research Articles

Methylphenidate enhances memory consolidation and amplifies long-term potentiation: differential involvement of the prefrontal dopamine receptor and norepinephrine receptor

Methylphenidate enhances memory consolidation and amplifies long-term potentiation: differential involvement of the prefrontal dopamine receptor and norepinephrine receptor

Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex

Marijuana (Cannabis sativa) is one of the most widely used illicit drugs in the world. Its use is associated with impairments in cognitive function. We previously reported that Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive component of marijuana, impaired spatial working memory in the radial maze task when injected intracortically (IC) into the medial prefrontal cortex (mPFC) of rats. Here, we used this paradigm to evaluate the involvement of prefrontal dopamine receptors in working memory disruption induced by Δ9-THC. Intracortical pre-treatment of animals with either the D1- or D2-like dopamine receptor antagonists SCH 23390 or clozapine, respectively, significantly reduced the number of errors rats made in the radial maze following treatment with Δ9-THC also administered intracortically. These results were obtained in the absence of locomotor impairment, as evidenced by the time spent in each arm a rat visited. Our findings suggest that prefrontal dopamine receptors are involved in Δ9-THC-induced disruption of spatial working memory. This interaction between the cannabinoid system and dopamine release in the PFC contributes to new directions in research and to treatments for cognitive dysfunctions associated with drug abuse and dependence.

Rat prefrontal dopamine and cognitive control: Impaired and enhanced conflict performance.

It has been proposed that the cognitive dysfunction observed in patients with schizophrenia reflects a failure in cognitive control, in particular an inability to use task-relevant information to guide behavior. Using a prefrontal-dependent task designed to reflect aspects of cue and response conflict seen in human cognitive paradigms, we examined the influence of prefrontal dopamine receptor manipulation on the contextual control of response conflict. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two discriminably different contexts. At test, audiovisual compounds of these training stimuli were presented, in extinction, in each of the training contexts. These compounds were formed in such a way that the individual elements previously dictated different responses during training, termed incongruent trials. Studies have shown that rats use contextual information to disambiguate the conflicting information provided by incongruent compounds, responding in manner that is appropriate to the stimulus element that was trained in the test context. Direct infusion of the D1 receptor agonist SKF-38393 into the prelimbic cortex was found to modulate incongruent trial performance in a manner that was dependent upon baseline performance: animals in the low baseline group demonstrated improved incongruent performance following infusion of SKF-38393 into the prelimbic cortex. In contrast, high performers showed a reduction in accuracy during incongruent compounds. This paradigm provides a reliable framework for assessing the efficacy of preclinical agents in treating the cognitive impairments seen in frontal-related disorders such as schizophrenia.

The dopamine agonist apomorphine differentially affects cognitive performance in alcohol dependent patients and healthy controls

Background Reduced metabolic activity in frontal brain regions, and reduced striatal dopamine receptor densities have been shown in alcohol dependent patients. Little is known on functional changes in the fronto-striatal-thalamic dopaminergic neurocircuitry in these patients. The objective of this study was to assess sensitivity of prefrontal dopamine receptors in alcohol dependent patients. Experimental procedures Male alcohol dependent patients ( N = 40) and healthy controls ( N = 39) performed an AX-continuous performance test before and after administration of the DA agonist apomorphine (0.005 mg/kg). Results At baseline alcohol dependent patients were slower and less accurate compared to healthy controls. After administration of apomorphine, performance improved in alcohol dependent patients and deteriorated in healthy controls. Conclusions Reduced cognitive performance in alcohol dependent patients compared with healthy controls may indicate dopamine dysfunctioning at the prefrontal level. Improvement of cognitive performance in alcohol dependent patients after administration of apomorphine and deterioration in healthy controls provides evidence for an inverted U-shape relation between dopaminergic functioning and cognitive performance.

Periadolescent stress exposure exerts long-term effects on adult stress responding and expression of prefrontal dopamine receptors in male and female rats

Recent research has demonstrated that experiential/environmental factors in early life can program the adult stress response in rats, and this is manifest as altered hypothalamic-pituitary-adrenocortical activity and behavior in response to a stressor. Very little work has been devoted to investigating whether the environment during adolescence plays a similar role in modulating ongoing developmental processes and how this might affect adult stress responding. Periadolescent predator odor (PPO) exposure was used here as a naturalistic model of repeated psychological stress. Behavioral and endocrine responses to PPO changed across the exposure period, and behavioral alterations persisted into adulthood. While adolescent rats showed pronounced avoidance responses upon initial PPO exposure, hyperactivity increased across the exposure period, especially in females. Corticosterone (cort) responses to stressor exposure also changed in females, with higher physiological baseline levels observed at the end of the exposure period. In adulthood, relative to rats who had received a control manipulation during adolescence, PPO-exposed rats were more fearful in a novel open field and displayed altered responses to a predator odor stress test in adulthood. Moreover, lower levels of the D2 dopamine (DA) receptor were measured in prefrontal (infralimbic and dorsopeduncular) cortices of PPO-exposed rats. These findings suggest that the adolescent period may represent a sensitive period during which developmental programming of the stress response occurs.

Injection of apomorphine into the medial prefrontal cortex of the rat increases haloperidol-induced catalepsy

In the present study, the interaction between cortical and subcortical dopamine systems was further characterized. A catalepsy test was used to assess how stimulation of prefrontal dopamine receptors affects the behavior of naive rats or of rats systemically pretreated with a dopamine antagonist