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Biomedical subjects

Andreas Arvanitogiannis

Publications and source records attributed to Andreas Arvanitogiannis.

7 recordsLinked to original sources

Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical and behavioral consequences.

Extracellular dopamine levels were measured in the rat nucleus accumbens by means of in vivo microdialysis. Delivery of rewarding medial forebrain bundle stimulation at a low rate (5 trains/min) produced a sustained elevation of dopamine levels, regardless of whether train onset was predictable. When the rate of train delivery was increased to 40 trains/min, dopamine levels rose rapidly during the first 40 min but then declined toward the baseline range. The rewarding impact of the stimulation was reduced following prior delivery of stimulation at the high, but not the low, rate. These results support the idea that dopamine tone plays an enabling role in brain stimulation reward and is elevated similarly by predictable and unpredictable stimulation.

Animals↗

Differential behavioral and neurochemical effects of cocaine after early exposure to methylphenidate in an animal model of attention deficit hyperactivity disorder.

We used a putative animal model of attention deficit hyperactivity disorder (ADHD), the SHR rat, to examine the effects of repeated exposure to methylphenidate (MPH; Ritalin) during the pubertal period on cocaine-induced conditioned place preference and dopamine (DA) levels in the nucleus accumbens (NAc) in adulthood. Our results indicate that early exposure to methylphenidate diminishes sensitivity to the incentive properties of cocaine in adulthood, but it does so without altering the response of the mesolimbic dopamine system.

Age Factors↗

A role for affect in context-dependent sensitization to amphetamine.

Repeated exposure to stimulant drugs, such as amphetamine, induces sensitization to their behavioral activating effects. It is commonly assumed that behavioral sensitization is expressed in the environment explicitly paired with the drug but not in a different environment explicitly unpaired with the drug. The experiments reported here show that this assumption is incorrect. It was found that sensitization was expressed in an environment explicitly unpaired with amphetamine, but imbued with positive affective valence by its association with a natural reward, oral sucrose. These results suggest that the affective valence of the environment in which the drug is administered plays a decisive role in the expression of drug effects, regardless of any previous association of that environment with the drug.

Amphetamine↗

Elevated expression of 5-HT1B receptors in nucleus accumbens efferents sensitizes animals to cocaine.

Although the effects of psychostimulants on brain dopamine systems are well recognized, the direct actions of cocaine on serotonin systems also appear to be important to its addictive properties. For example, serotonin actions at 5-HT1B receptors in the ventral tegmental area (VTA) modulate cocaine-induced dopamine release in the nucleus accumbens (NAcc) and alter the rewarding and stimulant properties of cocaine. However, the mechanisms of these effects have been unclear, because several neuron types in VTA express 5-HT1B receptors. One possibility is that 5-HT1B receptors on the terminals of GABAergic projections from NAcc to VTA inhibit local GABA release, thereby disinhibiting VTA neurons. We tested this hypothesis directly by using viral-mediated gene transfer to overexpress 5-HT1B receptors in NAcc projections to VTA. A viral vector containing either epitope hemagglutinin-tagged 5-HT1B and green fluorescent protein (HA1B-GFP) cassettes or green fluorescent protein cassette alone (GFP-only) was injected into the NAcc shell, which sends projections to the VTA. HA1B-GFP injection induced elevated expression of 5-HT1B receptors in neuronal fibers in VTA and increased cocaine-induced locomotor hyperactivity without affecting baseline locomotion. Overexpression of 5-HT1B receptors also shifted the dose-response curve for cocaine-conditioned place preference to the left, indicating alterations in the rewarding effects of cocaine. Thus, increased expression of 5-HT1B receptors in NAcc efferents, probably in the terminals of medium spiny neurons projecting to the VTA, may contribute to psychomotor sensitization and offer an important target for regulating the addictive effects of cocaine.

Animals↗

Altered responsiveness to cocaine in rats exposed to methylphenidate during development.

Evidence in laboratory animals indicates that exposure to stimulants produces sensitization to their rewarding effects, a process that in humans would be expected to increase the risk of substance abuse. However, therapeutic administration of stimulants such as methylphenidate (MPH) in children with attention deficit hyperactivity disorder reportedly reduces the risk of substance abuse. Here we show in rats that exposure to MPH during pre-adolescence causes behavioral and neurobiological adaptations that endure into adulthood, and that are consistent with increased sensitivity to the aversive effects of cocaine.

Adaptation, Physiological↗