The inhibitory effects of AVP-mediated modulation of GABA release onto CA1 pyramidal neurons were overwhelmed by its strong excitation of CA1 pyramidal neurons in physiological condition but revealed when its direct excitation of the pyramidal neurons was blocked suggesting that AVP-mediated modulation of GABAergic transmission fine-tunes the excitability

of CA1 pyramidal neurons. (c) 2012 Elsevier Ltd. All rights reserved.”
“In humans, exposure to environmental contexts previously associated with heroin intake can provoke relapse to drug use. In rats, exposure to heroin-associated contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by blockade of Salubrinal in vitro D-1-family receptors in lateral or medial accumbens shell, but not accumbens core.

In this study, we further characterized the role of striatal D-1-family receptors in context-induced reinstatement by assessing the effect of dorsolateral or dorsomedial injections of the D-1-family receptor antagonist SCH 23390 on GSK1904529A this reinstatement.

Rats were trained to self-administer heroin (0.05-0.10 mg/kg per infusion) for 12 days; drug infusions were paired with a discrete tone-light cue. Subsequently, heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a nondrug context.

During reinstatement tests under extinction conditions, the D-1-family receptor antagonist SCH 23390 (0.3-1.0 A mu g per side) was injected into the dorsolateral or dorsomedial striatum prior to exposure to heroin self-administration context or the nondrug (extinction)

context. We then used a disconnection procedure to examine whether D-1-family receptors in the dorsolateral striatum and lateral accumbens shell jointly or independently U0126 support context-induced reinstatement.

Dorsolateral but not dorsomedial SCH 23390 injections attenuated context-induced reinstatement of heroin seeking. SCH 23390 injections into the dorsolateral striatum of one hemisphere and lateral accumbens shell of the other hemisphere were ineffective.

Results indicate that dorsolateral striatum D-1-family dopamine receptors are critical for context-induced reinstatement of heroin seeking. Results also suggest that D-1-receptor-mediated dopamine transmission in the dorsolateral striatum and lateral accumbens shell independently support this reinstatement.”
“Signal transduction cascades, including the MAPK, PI3 kinase, Ca2+ and PKC pathways, play important roles in neurons downstream of multiple signals including neurotrophins and neurotransmitters. Small molecule kinase inhibitors that block these pathways provide a powerful way of studying the in vivo or cellular roles of these signaling systems.