Differential regulation of cocaine-induced locomotor activity in inbred long-sleep and short-sleep mice by dopamine and serotonin systems.
Acute injection of cocaine increases locomotor activity of inbred long-sleep (ILS) mice to a greater extent than inbred short-sleep (ISS) mice. Strain differences in dopamine and/or serotonin (5-HT) neurotransmission could underlie these behavioral differences. Here, we found that dopamine D1, 5-HT(2A) and 5-HT3 receptor antagonists reduced cocaine-stimulated activity selectively in ILS mice. In contrast, 5-HT transporter (SERT) or 5-HT(1A) receptor antagonists potentiated cocaine-stimulated activity in ISS, but not in ILS, mice; this potentiation in ISS mice was abolished by dopamine D1 receptor blockade. Thus, in ILS mice, cocaine-induced activation of D1, 5-HT(2A) or 5-HT3 receptors is sufficient to produce locomotor stimulation. In contrast, ISS mice require pharmacologically increased 5-HT levels, which appear to result in increased dopamine neurotransmission, for cocaine-induced activation. Our results demonstrate strain differences in dopamine/5-HT receptor subtypes and their interactions that contribute to the differential behavioral responsiveness of ILS and ISS mice to cocaine.
Hanania
Taleen
T
Department of Pharmacology and Neuroscience Program, University of Colorado Health, Sciences Center, Denver, CO, USA. taleen.hanania@psychogenetics.com
McCreary
Andrew C
AC
Salaz
Danielle O
DO
Lyons
Anne M
AM
Zahniser
Nancy R
NR
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics / Q000502:physiology*; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects* / Q000235:genetics*; D013045:Species Specificity
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D003042:Cocaine