Adrenergic and noradrenergic innervation of the midbrain ventral tegmental area and retrorubral field: prominent inputs from medullary homeostatic centers.

Adrenergic agents modulate the activity of midbrain ventral tegmental area (VTA) neurons. However, the sources of noradrenergic and adrenergic inputs are not well characterized. Immunostaining for dopamine beta-hydroxylase revealed fibers within dopamine (DA) neuron areas, with the highest density in the retrorubral field (A8 cell group), followed by the VTA (A10 cell group), and very few fibers within substantia nigra compacta.

Neurophysiological actions of methylphenidate in the primary somatosensory cortex.

As a catecholamine reuptake blocker, methylphenidate (MPH) enhances noradrenergic transmission and is likely to influence norepinephrine actions in sensory systems. To characterize neurophysiological actions of MPH in the primary somatosensory (SI) cortex, we recorded basal and whisker deflection-evoked discharge of infragranular sensory cortical neurons, before and after intraperitoneal administrations of saline and MPH (5 mg/kg) in halothane-anesthetized rats. MPH had two types of actions on sensory-evoked neuronal responses in the SI cortex, depending on the initial amplitude of the sensory response.

Methylphenidate enhances noradrenergic transmission and suppresses mid- and long-latency sensory responses in the primary somatosensory cortex of awake rats.

Noradrenergic neurons send widespread projections to sensory networks throughout the brain and regulate sensory processing via norepinephrine (NE) release. As a catecholamine reuptake blocker, methylphenidate (MPH) is likely to interact with noradrenergic transmission and NE modulatory action on sensory systems. To characterize the neurochemical actions of MPH in the primary sensory cortex of freely behaving rats and their consequences on sensory processing, we measured extracellular NE levels in the primary somatosensory (SI) cortex by microdialysis and recorded basal and sensory-evoked discharge of infragranular SI cortical neurons, before and after intraperitoneal administrations of saline or MPH (1 and 5 mg/kg).

5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.

Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of alpha1b-adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an alpha1-adrenergic antagonist.

Cocaine-induced vs. behaviour-related alterations of spontaneous and evoked discharge of somatosensory cortical neurons.

While the abuse potential of cocaine stems mainly from its ability to increase dopaminergic transmission in limbic regions, drug actions on other monoamine-innervated circuits may contribute to the development and maintenance of cocaine addiction. Previous extracellular recordings in anaesthetized rats revealed a facilitatory influence of cocaine on primary sensory pathways, which could influence the processing of drug-related stimuli during the development of cocaine addiction. We further analysed these sensory effects of cocaine in freely behaving rats (n = 9).

Stimulation of postsynaptic alpha1b- and alpha2-adrenergic receptors amplifies dopamine-mediated locomotor activity in both rats and mice.

Recent experiments have shown that mice lacking the alpha1b-adrenergic receptor (alpha1b-AR KO) are less responsive to the locomotor hyperactivity induced by psychostimulants, such as D-amphetamine or cocaine, than their wild-type littermates (WT). These findings suggested that psychostimulants induce locomotor hyperactivity not only because they increase dopamine (DA) transmission, but also because they release norepinephrine (NE). To test whether NE release could increase DA-mediated locomotor hyperactivity, rats were treated with GBR 12783 (10 mg/kg), a specific inhibitor of the DA transporter, and NE release was enhanced with dexefaroxan (0.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results.

Critical role of alpha1-adrenergic receptors in acute and sensitized locomotor effects of D-amphetamine, cocaine, and GBR 12783: influence of preexposure conditions and pharmacological characteristics.

Psychostimulant-induced locomotor hyperactivity is commonly associated with an inhibition of dopamine reuptake. However, a physiological coupling between noradrenergic and dopaminergic neurons occurring through the stimulation of alpha1-adrenergic receptors has recently been proposed. This possibility was tested on locomotor responses induced either by D-amphetamine and cocaine, which both interfere with noradrenergic and dopaminergic transmissions, or by GBR 12783, a specific dopamine reuptake inhibitor.