D1 and D2 dopamine receptors differentially increase Fos-like immunoreactivity in accumbal projections to the ventral pallidum and midbrain.
Alterations in dopaminergic neurotransmission have profound effects on neuronal expression of the putative activity marker, Fos, in both the dorsal and ventral striatum. Stimulants such as D-amphetamine and cocaine increase Fos-like immunoreactivity by enhancing the activation of D1 dopamine receptors. In contrast, neuroleptics such as haloperidol and raclopride increase Fos-like immunoreactivity by blocking striatal D2 dopamine receptors. In the dorsal striatum, D1 receptor stimulation elevates Fos-like immunoreactivity predominantly in neurons projecting to the midbrain (substantia nigra), whereas D2 receptor antagonism enhances Fos-like immunoreactivity principally in neurons projecting to the pallidum (globus pallidus). These findings are consistent with the proposal that D1 receptors are located chiefly on striatonigral neurons, whereas D2 receptors reside mainly on striatopallidal neurons. Since the nucleus accumbens (largest component of the ventral striatum) also sends projections to the midbrain (ventral tegmental area and substantia nigra) and pallidum (ventral pallidum), the present study utilized retrograde tract-tracing techniques to determine if there was a similar segregation of D1 agonist- and D2 antagonist-induced Fos-like immunoreactivity in these accumbal projections. In addition, we examined whether these relationships were the same in the core and shell regions of the nucleus accumbens. Like the dorsal striatum, D1 agonists (D-amphetamine and CY 208-243), but not D2 antagonists (haloperidol and clozapine), increased Fos-like immunoreactivity in accumbal neurons projecting to the midbrain (ventral tegmental area and substantia nigra). Also like the dorsal striatum, D2 antagonist-induced Fos-like immunoreactivity was located preferentially in accumbal neurons projecting to the pallidum (ventral pallidum). However, unlike the dorsal striatum, where the vast majority of neurons which display D1 agonist-induced Fos-like immunoreactivity project to the midbrain, nearly 50% of those neurons in the nucleus accumbens which were Fos-immunoreactive after D-amphetamine or CY 208-243 projected to the ventral pallidum. Thus, a similar number of accumbal neurons which expressed D1 agonist-induced Fos-like immunoreactivity were retrogradely labelled from the midbrain and ventral pallidum. Accumbal projections to the midbrain and ventral pallidum were retrogradely labelled with different retrograde tracers in order to determine the degree of collateralization between these pathways. Approximately 20% of retrogradely labelled neurons displayed both tracers, indicating that collateralization and damage to fibres of passage could not account for all of those cases in which D1 agonist-induced Fos-like immunoreactivity was detected in accumbal neurons projecting to the ventral pallidum.(ABSTRACT TRUNCATED AT 400 WORDS)
Robertson
G S
GS
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Jian
M
M
D000818:Animals; D003024:Clozapine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000502:physiology; D009714:Nucleus Accumbens / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003024:Clozapine; D006220:Haloperidol