A considerable research effort has been made to characterize the central effects of the opioids in terms of brain catecholamine neurotransmission. However, the mesocorticolimbic dopamine system, which has neuronal perikarya in the ventral tegmental area and axonal terminals in the nucleus accumbens, has not been studied to a great extent in this regard. The first objective of this proposal is to characterize the effects of opioids on mesocorticolimbic dopamine function. This will be performe by acute microinjection of opioid into the ventral tegmental area or nucleus accumbens of the rat. After microinjection, I will assess effects on the mesocorticolimbic dopamine system by neurochemical measurements of dopamine release, synthesis and turnover, and by behavioral measurements of motor activity. The effects of peripherally administered opioids will then be compared with the effects of intracranially administered opioids. In addition to the opioids, the indirect sympathomimetics, cocaine and amphetamine, have been shown to affect mesocorticolimbic dopamine function. Therefore, a second objective of this proposal is to evaluate an interaction between the opioids and cocaine and amphetamine. Again, microinjection of drugs into the ventral tegmental area or nucleus accumbens, followed by neurochemical and behavioral measurements shall be used to evaluate a potential interaction. Daily administration with amphetamine or cocaine causes a progressive increase in the mesocorticolimic-mediated behavioral and neurohemical effects produced by these drugs. It has also been found that daily injection with opioid into the ventral tegmental area produces a progressive increase in mesocorticolimbic-mediated responses. Thus, as a third objective of this proposal, I will evaluate an interaction between the opioids, amphetamine and cocaine in this behavioral and neurochemical """"""""sensitization"""""""" phenomenon. These studies will provide insight into how the opioids affect the mesocorticolimbic dopamine system. It also evaluates an interaction between the acute and chronic administration of the opioids and the commonly abused sympathomimetics, cocaine and amphetamine. Not only have some studies implicated the involvement of the mesocorticolimbic dopamine system in the reinforcing properties of the opioids, cocaine and amphetamine, but the use of these drugs in combination in our society is becoming an increasingly severe social problem.
| Roberts-Wolfe, Douglas; Bobadilla, Ana-Clara; Heinsbroek, Jasper A et al. (2018) Drug Refraining and Seeking Potentiate Synapses on Distinct Populations of Accumbens Medium Spiny Neurons. J Neurosci 38:7100-7107 |
| Spencer, Sade; Neuhofer, Daniela; Chioma, Vivian C et al. (2018) A Model of ?9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens. Biol Psychiatry 84:601-610 |
| Neuhofer, Daniela; Kalivas, Peter (2018) Metaplasticity at the addicted tetrapartite synapse: A common denominator of drug induced adaptations and potential treatment target for addiction. Neurobiol Learn Mem 154:97-111 |
| Bobadilla, Ana-Clara; Heinsbroek, Jasper A; Gipson, Cassandra D et al. (2017) Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior. Prog Brain Res 235:93-112 |
| Spencer, Sade; Kalivas, Peter W (2017) Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse. Int J Neuropsychopharmacol 20:797-812 |
| Kupchik, Yonatan M; Kalivas, Peter W (2017) The Direct and Indirect Pathways of the Nucleus Accumbens are not What You Think. Neuropsychopharmacology 42:369-370 |
| Smith, Alexander C W; Scofield, Michael D; Heinsbroek, Jasper A et al. (2017) Accumbens nNOS Interneurons Regulate Cocaine Relapse. J Neurosci 37:742-756 |
| Taniguchi, Makoto; Carreira, Maria B; Cooper, Yonatan A et al. (2017) HDAC5 and Its Target Gene, Npas4, Function in the Nucleus Accumbens to Regulate Cocaine-Conditioned Behaviors. Neuron 96:130-144.e6 |
| Brown, Robyn Mary; Kupchik, Yonatan Michael; Spencer, Sade et al. (2017) Addiction-like Synaptic Impairments in Diet-Induced Obesity. Biol Psychiatry 81:797-806 |
| Bobadilla, Ana-Clara; Garcia-Keller, Constanza; Heinsbroek, Jasper A et al. (2017) Accumbens Mechanisms for Cued Sucrose Seeking. Neuropsychopharmacology 42:2377-2386 |
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