The anterior subventricular zone (SVZa) is the site for postnatal neurogenesis of interneurons of the olfactory bulb (OB). Concurrently or after proliferation, neuronal precursors therein migrate within it to reach the OB, an event known as the rostral migratory stream (RMS). We used bromodeoxyuridine (BrdU) incorporation with short survival times to investigate the distribution of S-phase nuclei in the SVZa/RMS of the postnatal mouse. We observed that they were distributed along a radial, outside-in, decreasing gradient that persisted until postnatal day 10 (P10), then faded away to finally disappear by P16. After longer post-injection survival times labeled cell distribution became homogeneous. GFAP-positive glia are present at the periphery but not at the core of the SVZa. Our results represent the first evidence of a discrete spatial organization of a cell cycle phase within the SVZ, and also suggests a segregation of proliferating and migrating cells in the rostral migratory stream of the early postnatal mouse.
High doses of apomorphine induce sensitization to locomotor stimulant effects whereas low doses induce locomotor inhibition. We examined whether repeated low dose apomorphine induced sensitization and conditioning to the locomotor inhibitory effect. Three doses of the D1/D2 agonist, apomorphine, were used in a Pavlovian conditioning protocol: 0.05 mg/kg (autoreceptor level), 0.5 and 2.0 mg/kg (post-synaptic level). Rats received 5 daily apomorphine treatments paired or unpaired to an open-field environment (conditioning phase) followed by a saline test (conditioning test) and an apomorphine challenge test (sensitization test). Locomotion was measured for 30 min. During the acquisition phase, the 0.05 mg/kg paired treatment decreased locomotion while the high dose paired treatments increased locomotion. The 0.05 mg/kg paired treatment did not induce conditioning but induced inhibitory locomotor sensitization. The post-synaptic paired treatments produced conditioned and sensitized locomotor stimulation. For the low dose results, we propose an expanded contextual stimulus, which includes interoceptive drug cues. In the sensitization test, the same interoceptive drug cues and test environment cues are present as those during acquisition. In the conditioning test, normative dopaminergic activity is present which generates internal cues that may or may not generalize to the drug-induced cues and, permit or prevent retrieval of conditioning.
The SCH-23390 findings are supportive of a critical role for D1 receptors in apomorphine effects whereas the sulpiride effects diminish the importance of conditioning and dopamine autoreceptor subsensitivity mechanisms in the mediation of apomorphine sensitization.
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