Functional correlation between GABAergic and dopaminergic systems of dorsal hippocampus and ventral tegmental area in passive avoidance learning in rats

Neuroscience. 2011 Nov 24;196:104-14. doi: 10.1016/j.neuroscience.2011.08.073. Epub 2011 Sep 10.

Abstract

The aim of the present study was to investigate the existence of possible functional correlation between GABA-A and dopamine (DA) receptors of the dorsal hippocampus and the ventral tegmental area (VTA) in passive avoidance learning. Two guide cannulas were stereotaxically implanted in the CA1 region of the dorsal hippocampus and the VTA of male Wistar rats. In order to measure memory retrieval, the animals were trained in a step-through type passive avoidance task and tested 24 h after training. Post-training intra-CA1 administration of a GABA-A receptor agonist, muscimol (0.01-0.02 μg/rat) dose-dependently impaired memory retrieval. Post-training intra-VTA administration of SCH23390 (a dopamine D1 receptor antagonist; 0.1-0.8 μg/rat) or sulpiride (a D2 receptor antagonist; 0.5-1.5 μg/rat) decreased the inhibitory effect of muscimol (0.02 μg/rat, intra-CA1) on memory retrieval. Intra-VTA administration of the same doses of SCH23390, but not sulpiride, decreased the step-through latencies. On the other hand, post-training administration of muscimol (0.02 μg/rat) into the VTA inhibited memory retrieval. The administration of SCH23390 (0.01-0.2 μg/rat) or sulpiride (0.1-1 μg/rat) into the CA1 region, immediately after training, had no effect on memory retrieval. Furthermore, the amnesic effect of intra-VTA administration of muscimol was significantly decreased by intra-CA1 administration of sulpiride (0.5 and 1 μg/rat, intra-CA1), but not SCH23390. The practical conclusion is that the relationship between the hippocampus and the VTA may regulate memory formation in passive avoidance learning. Also, the correlation between the hippocampus and VTA by a dopaminergic system may be involved in mediating muscimol-induced amnesia.

MeSH terms

  • Amnesia / chemically induced
  • Amnesia / drug therapy
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / physiology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • GABA-A Receptor Agonists / administration & dosage
  • GABA-A Receptor Agonists / pharmacology
  • GABAergic Neurons / physiology*
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Microinjections
  • Muscimol / administration & dosage
  • Muscimol / antagonists & inhibitors
  • Muscimol / pharmacology
  • Rats
  • Rats, Wistar
  • Sulpiride / administration & dosage
  • Sulpiride / pharmacology
  • Sulpiride / therapeutic use
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology*

Substances

  • Benzazepines
  • Dopamine Antagonists
  • GABA-A Receptor Agonists
  • SCH 23390
  • Muscimol
  • Sulpiride