6-cyano-7-nitroquinoxaline-2-3-dione and eticlopride

Dopamine is critical for higher neural processes and modifying the activity of the prefrontal cortex (PFC). However, the mechanism of dopamine contribution to the modification of neural representation is unclear. Using in vivo two-photon population Ca(2+) imaging in awake mice, this study investigated how neural representation of visual input to PFC neurons is regulated by dopamine. Phasic stimulation of dopaminergic neurons in the ventral tegmental area (VTA) evoked prolonged Ca(2+) transients, lasting ~30 s in layer 2/3 neurons of the PFC, which are regulated by a dopamine D1 receptor-dependent pathway. Furthermore, only a conditioning protocol with visual sensory input applied 0.5 s before the VTA dopaminergic input could evoke enhanced Ca(2+) transients and increased pattern similarity (or establish a neural representation) of PFC neurons to the same sensory input. By increasing both the level of neuronal response and pattern similarity, dopaminergic input may establish robust and reliable cortical representation.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Benzazepines; Calcium; Dopamine; Dopamine Antagonists; Dopaminergic Neurons; Electric Stimulation; Evoked Potentials, Visual; Mice; Mice, Inbred C57BL; Neural Pathways; Piperazines; Prefrontal Cortex; Receptors, Dopamine D1; Salicylamides; Stereotaxic Techniques; Synaptic Transmission; Ventral Tegmental Area; Wakefulness

Opioid receptors located on interneurons in the ventral tegmental area (VTA) inhibit GABA(A)-mediated synaptic transmission to dopamine projection neurons. The resulting disinhibition of dopamine cells in the VTA is thought to play a pivotal role in drug abuse; however, little is known about how this GABAA synapse is affected after chronic morphine treatment. The regulation of GABA release during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. Slices containing the VTA were prepared and maintained in morphine-free solutions, and GABAA IPSCs were recorded from dopamine cells. The amplitude of evoked IPSCs and the frequency of spontaneous miniature IPSCs measured in slices from morphine-treated guinea pigs were greater than placebo-treated controls. In addition, activation of adenylyl cyclase, with forskolin, and cAMP-dependent protein kinase, with Sp-cAMPS, caused a larger increase in IPSCs in slices from morphine-treated animals. Conversely, the kinase inhibitors staurosporine and Rp-CPT-cAMPS decreased GABA IPSCs to a greater extent after drug treatment. The results indicate that the probability of GABA release was increased during withdrawal from chronic morphine treatment and that this effect resulted from an upregulation of the cAMP-dependent cascade. Increased transmitter release from opioid-sensitive synapses during acute withdrawal may be one adaptive mechanism that results from prolonged morphine treatment.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Animals; Colforsin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dopamine; Dopamine Antagonists; Enzyme Activation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; GABA Antagonists; gamma-Aminobutyric Acid; Guinea Pigs; Interneurons; Morphine; Nerve Tissue Proteins; Organophosphorus Compounds; Patch-Clamp Techniques; Phorbol 12,13-Dibutyrate; Picrotoxin; Receptors, GABA-A; Salicylamides; Serotonin; Signal Transduction; Staurosporine; Strychnine; Substance Withdrawal Syndrome; Tegmentum Mesencephali; Thionucleotides