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Epinephrine increases contextual learning through activation of peripheral β2-adrenoceptors
- Source :
- Psychopharmacology. 233:2099-2108
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Phenylethanolamine-N-methyltransferase knockout (Pnmt-KO) mice are unable to synthesize epinephrine and display reduced contextual fear. However, the precise mechanism responsible for impaired contextual fear learning in these mice is unknown. Our aim was to study the mechanism of epinephrine-dependent contextual learning. Wild-type (WT) or Pnmt-KO (129x1/SvJ) mice were submitted to a fear conditioning test either in the absence or in the presence of epinephrine, isoprenaline (non-selective β-adrenoceptor agonist), fenoterol (selective β2-adrenoceptor agonist), epinephrine plus sotalol (non-selective β-adrenoceptor antagonist), and dobutamine (selective β1-adrenoceptor agonist). Catecholamines were separated by reverse-phase HPLC and quantified by electrochemical detection. Blood glucose was measured by coulometry. Re-exposure to shock context induced higher freezing in WT and Pnmt-KO mice treated with epinephrine and fenoterol than in mice treated with vehicle. In addition, freezing response in Pnmt-KO mice was much lower than in WT mice. Freezing induced by epinephrine was blocked by sotalol in Pnmt-KO mice. Epinephrine and fenoterol treatment restored glycemic response in Pnmt-KO mice. Re-exposure to shock context did not induce a significant difference in freezing in Pnmt-KO mice treated with dobutamine and vehicle. Aversive memories are best retained if moderately high plasma epinephrine concentrations occur at the same moment as the aversive stimulus. In addition, epinephrine increases context fear learning by acting on peripheral β2-adrenoceptors, which may induce high levels of blood glucose. Since glucose crosses the blood–brain barrier, it may enhance hippocampal-dependent contextual learning.
- Subjects :
- 0301 basic medicine
Agonist
endocrine system
medicine.medical_specialty
Epinephrine
medicine.drug_class
Adrenergic beta-Antagonists
Context (language use)
Mice
03 medical and health sciences
0302 clinical medicine
Adrenergic beta-2 Receptor Antagonists
Dobutamine
Isoprenaline
Internal medicine
medicine
Animals
Learning
Fear conditioning
Adrenergic beta-2 Receptor Agonists
Fenoterol
Mice, Knockout
Pharmacology
Chemistry
Phenylethanolamine N-Methyltransferase
Sotalol
Isoproterenol
Antagonist
Fear
Adrenergic beta-Agonists
Phenylethanolamine N-methyltransferase
Glucose
030104 developmental biology
Endocrinology
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 233
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....c299647e5909cef7f3028779271b6e54