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1.
J Neurosci ; 39(3): 503-518, 2019 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-30446532

RESUMEN

Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male rats, querying the roles of DA neuron inhibitory and excitatory G-protein signaling in these processes. Designer receptor stimulation of Gq signaling, but not Gs signaling, in DA neurons enhanced cocaine seeking via functionally distinct projections to forebrain limbic regions. In contrast, engaging inhibitory Gi/o signaling in DA neurons blunted the reinforcing and priming effects of cocaine, reduced stress-potentiated reinstatement, and altered behavioral strategies for cocaine seeking and taking. Results demonstrate that DA neurons play several distinct roles in cocaine seeking, depending on behavioral context, G-protein-signaling cascades, and DA neuron efferent targets, highlighting their multifaceted roles in addiction.SIGNIFICANCE STATEMENT G-protein-coupled receptors are crucial modulators of ventral tegmental area (VTA) dopamine neuron activity, but how this metabotropic signaling impacts the complex roles of dopamine in reward and addiction is poorly understood. Here, we bidirectionally modulate dopamine neuron G-protein signaling with DREADDs (designer receptors exclusively activated by designer drugs) during a variety of cocaine-seeking behaviors, revealing nuanced, pathway-specific roles in cocaine reward, effortful seeking, and relapse-like behaviors. Gq and Gs stimulation activated dopamine neurons, but only Gq stimulation robustly enhanced cocaine seeking. Gi/o inhibitory signaling reduced some, but not all, types of cocaine seeking. Results show that VTA dopamine neurons modulate numerous distinct aspects of cocaine addiction- and relapse-related behaviors, and point to potential new approaches for intervening in these processes to treat addiction.


Asunto(s)
Trastornos Relacionados con Cocaína/genética , Trastornos Relacionados con Cocaína/fisiopatología , Neuronas Dopaminérgicas/efectos de los fármacos , Área Tegmental Ventral/fisiopatología , Animales , Conducta Animal , Trastornos Relacionados con Cocaína/psicología , Comportamiento de Búsqueda de Drogas , Proteínas de Unión al GTP/fisiología , Sistema Límbico/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Prosencéfalo/efectos de los fármacos , Ratas , Ratas Transgénicas , Recurrencia , Recompensa , Autoadministración , Transducción de Señal/efectos de los fármacos , Estrés Psicológico/psicología , Área Tegmental Ventral/efectos de los fármacos
2.
Cureus ; 15(9): e45424, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37724100

RESUMEN

Latissimus dorsi (LD) tendon rupture is a rare injury that occurs in athletes throughout a wide range of sports, including baseball, rock climbing, tennis, and golf. LD tendon repair requires analgesia in nerve distributions from C5-T6. A 33-year-old man presented for right LD tendon repair after rock climbing eight weeks prior to the operation. An interscalene nerve block catheter was placed preoperatively for postoperative pain control. After induction of general endotracheal anesthesia, a mid-axillary incision was made down to the sixth rib and the patient underwent LD tendon repair. Postoperatively, the patient reported decreased pinprick sensation at the shoulder but pain along the mid-axillary incision. The erector spinae plane block was placed at the T3 level and pain relief was achieved within 20 minutes. This case report demonstrates that the erector spinae plane block serves as a useful adjunct to the brachial plexus block in surgeries involving the LD tendon.

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