Evidence suggests that nicotine and alcohol can each serve as a gateway drug. We determined whether prior treatment would alter amphetamine reward. Also, we examined age dopaminergic neurotransmission are important in this regard. Male female adolescent adult C57BL/6J mice were tested for baseline place preference. Mice then received six conditioning with saline/nicotine (0.25 mg/kg) twice dail...

The present study demonstrates that repeated administration of SKF-38393, a D1-dopamine agonist, is necessary for maximal behavioral supersensitivity of D1-dopamine receptor responses in neonatal 6-OHDA-lesioned rats, confirming earlier work. This repeated administration of SKF-38393, which is referred to as priming of D1-dopamine receptor responses, resulted in a progressive increase in locomo...

It is generally assumed that the coupling of dopamine D1 receptors to adenylyl cyclase is mediated by the stimulatory GTP-binding protein Gs. However, the striatum contains little Gsa subunit, whereas it expresses high levels of Golfa, a close relative of Gsa that is also expressed in olfactory receptor neurons. We used Golfa knockout mice to examine the functional coupling of D1 receptors. We ...

Dopamine, by activating dopamine D1-type receptors, and adenosine, by activating adenosine A(2A) receptors, stimulate phosphorylation of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of M(r) 32,000) at Thr-34. In this study, we investigated the effect of metabotropic glutamate (mGlu) receptors on DARPP-32 phosphorylation at Thr-34 in neostriatal slices. A broad-spectrum mGlu receptor ag...

Dopamine activates phospholipase C in discrete regions of the mammalian brain, and this action is believed to be mediated through a D1-like receptor. Although multiple lines of evidence exclude a role for the D1 subtype of D1-like receptors in the phosphoinositide response, the D5 subtype has not been similarly examined. Here, mice lacking D5 dopamine receptors were tested for dopamine agonist-...

Dopamine receptors are members of the G protein-coupled receptor superfamily and play important roles in neuronal transmission. A D1-D2 receptor heterooligomer generating a Gprotein linked PLC-dependent intracellular calcium signal was previously identified. The discovery of this dopamine mediated calcium signal implicated a direct link between dopamine receptors and calcium generation, but its...

D1/D5 dopamine receptors in basal ganglia, hippocampus, and cerebral cortex modulate motor, reward, and cognitive behavior. Previous work with recombinant proteins revealed that in cells primed with heterologous G(q/11)-coupled G-protein-coupled receptor (GPCR) agonists, the typically G(s)-linked D1/D5 receptors can stimulate robust release of calcium from internal stores when coexpressed with ...

Contralateral turning was produced by unilateral injection of carbachol (0.5, 2.5, 5 micrograms) into the nucleus accumbens, but not into the dorsal or ventral striatum. This behaviour was inhibited by muscarinic M1 acetylcholine receptor blockade in the nucleus accumbens, and less effectively by blockade of muscarinic M2 and nicotinic acetylcholine receptors. Unilateral injection of a mixture ...

Previous studies have demonstrated that the effects of methamphetamine (METH) on dopaminergic and serotonergic systems are likely related to METH-induced increases in dopamine release. The ability of haloperidol to prevent these effects of METH suggests that dopamine receptor activation is involved in mediating these METH actions. The present studies were undertaken to determine what role the d...

LEK-8829 [9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8- aminomethylergoline bimaleinate] is an antagonist of dopamine D2 receptors and serotonin (5-HT)2 and 5-HT1A receptors in intact animals and a D1 receptor agonist in dopamine-depleted animals. In the present study, we used rats with unilateral striatal lesions with ibotenic acid (IA) to investigate the dopamine receptor activities of LEK...