Psychoactive drugs and regulation of the cAMP/PKA/DARPP-32 cascade in striatal medium spiny neurons.
Changes in activity of the medium spiny neurons (MSNs) of dorsal and ventral striatum result in alterations of motor performance, ranging from rapid increases or decreases in locomotor activity, to long-term modifications of motor behaviours. In the dorsal striatum, MSNs can be distinguished based on the organization of their connectivity to substantia nigra pars reticulata (SNpr) and internal segment of the globus pallidus (GPi), which, in turn, control thalamocortical neurons. Approximately half of the MSNs project directly to SNpr and GPi, their activation leading to disinhibition of thalamocortical neurons and increased motor activity. The other subpopulation of MSNs connects to SNpr and GPi indirectly and when activated promotes inhibition of thalamocortical neurons, thereby reducing motor activity. The dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is a modulator of the cAMP signalling pathway, highly expressed in MSNs. This review discusses the regulation of DARPP-32 exerted by psychoactive substances in specific populations of striatal projection neurons and its involvement in short- and long-term motor responses.
Borgkvist
Anders
A
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden.
Fisone
Gilberto
G
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D002186:Cannabinoids; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D011619:Psychotropic Drugs; D002110:Caffeine; D000661:Amphetamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003042:Cocaine