Abstract The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a growth factor that belongs to the transforming factor-beta (TGF-beta) superfamily and plays central role in multiple cell-cell signaling events throughout development. Through genetic screens we are seeking identify other functions act upstream, downstream or concert with dpp mediate its role. We report here characterization cloning Mothers against (Mad), identified two such screens. Mad loss-of-function mutations...

The development of diet-induced obesity (DIO) can potently alter multiple aspects dopamine signaling, including transporter (DAT) expression and reuptake. However, the time-course changes in DAT function whether such are dependent upon DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 6 weeks. Following exposure, were anesthetized with urethane striatal was assessed by electrically stimulating cell bodies ventral tegmental area (VTA) recording resultant...

ABSTRACT The proteins necessary for signal transduction in cells responding to ligands of the TGF-β family are largely unknown. We have previously identified Mad (Mothers against dpp), a gene that interacts with member encoded by decapentaplegic (dpp) Drosophila. Assay Mad’s role DPP-dependent events embryonic midgut development demonstrates is required any response visceral mesoderm or endoderm DPP signals from mesoderm. Replacement normal promoter heterologous (hsp70) fails restore...

Dependence is a hallmark feature of opiate addiction and defined by the emergence somatic affective withdrawal signs. The nucleus accumbens (NAc) integrates dopaminergic glutamatergic inputs to mediate rewarding aversive properties opiates. Evidence suggests that AMPA glutamate-receptor-dependent synaptic plasticity within NAc underlies aspects addiction. However, degree which receptors (AMPARs) contribute signs not fully understood. Here, we show microinjection AMPAR antagonist NBQX into...

The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c- fos mRNA in dorsal lateral region striatum produces an acute cataleptic response rodents that correlates with motor side effects haloperidol humans. Mice harboring a targeted disruption RIIβ subunit protein kinase A have profound deficit cAMP-stimulated activity striatum. When treated mutant mice fail to induce either or is blocked. However, both wild-type become when peptide directly injected into ventricle,...

The nucleus accumbens (NAc) is a critical brain area for reward and motivated behavior. Accumulating evidence suggests that altered function of the transcription factor cAMP response element binding protein (CREB) within NAc involved in depressive In rats, stress activates CREB NAc, elevation expression this region produces depressive-like behaviors are accompanied by activation CREB-regulated target genes. seem to be due, at least part, CREB-mediated increases dynorphin function, because...

Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY) conjugated to carrier protein keyhole limpet hemocyanin (OXY-KLH) has been shown attenuate antinociceptive effects of oxycodone. Here, vaccine's ability prevent acquisition intravenous (i.v.) oxycodone self-administration was studied rats. Effects vaccination on oxycodone-induced changes expression several genes within mesolimbic system, which are regulated by chronic opiate use,...

Motor stereotypies are abnormally repetitive behaviors that can develop with excessive dopaminergic stimulation and features of some neurologic disorders. To investigate the mechanisms required for induction stereotypy, we examined responses dopamine-deficient (DD) mice to increasing doses dopamine precursor l -DOPA. DD lack ability synthesize (DA) specifically in neurons yet exhibit robust hyperlocomotion relative wild-type (WT) when treated -DOPA, which restores striatal DA tissue content...

Morphine dependence is characterized by somatic and motivational signs of withdrawal that likely contribute to the maintenance addictive behavior. The nucleus accumbens (NAc) receives extensive dopaminergic input an important substrate for mediating these aversive states. In NAc, function transcription factor cAMP response element binding protein (CREB) AMPA glutamate receptor subunit, type 1 (GluR1) can be regulated dopamine (DA) D₁ receptor-mediated phosphorylation (P-CREB,...