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1.
Behav Brain Res ; 314: 125-33, 2016 11 01.
Article in English | MEDLINE | ID: mdl-27498247

ABSTRACT

About 40% of the dorsal raphe nucleus (DRN) neurons co-express serotonin (5-HT) and galanin. Serotonergic pathways from the DRN to the amygdala facilitate learned anxiety, while those from the DRN to the dorsal periaqueductal grey matter (DPAG) impair innate anxiety. Previously, we showed that galanin infusion in the DRN of rats induces anxiolytic effect by impairing inhibitory avoidance without changing escape behaviour in the elevated T-maze (ETM). Here, we evaluated: (1) which galanin receptors would be involved in the anxiolytic effect of galanin in the DRN of rats tested in the ETM; (2) the effects of galanin intra-DRN on panic-like behaviours evoked by electrical stimulation of the DPAG. The activation of DRN GAL1 receptors by M617 (1.0 and 3.0nmol) facilitated inhibitory avoidance, whereas the activation of GAL2 receptors by AR-M1896 (3.0nmol) impaired the inhibitory avoidance in the ETM, suggesting an anxiogenic and an anxiolytic-like effect respectively. Both agonists did not change escape behaviour in the ETM or locomotor activity in the open field. The anxiolytic effect of AR-M1896 was attenuated by the prior administration of WAY100635 (0.18nmol), a 5-HT1A antagonist. Galanin (0.3nmol) administered in the DRN increased discreetly flight behaviours induced by electrical stimulation of the DPAG, suggesting a panicolytic effect. Together, our results showed that galanin mediates opposite anxiety responses in the DRN by activation of GAL1 and GAL2 receptors. The anxiolytic effect induced by activation of Gal2 receptors may depend on serotonergic tone. Finally, the role of galanin in panic related behaviours remains uncertain.


Subject(s)
Anxiety/drug therapy , Dorsal Raphe Nucleus/drug effects , Galanin/pharmacology , Receptor, Galanin, Type 1/drug effects , Receptor, Galanin, Type 2/drug effects , Animals , Anti-Anxiety Agents/pharmacology , Anxiety/metabolism , Anxiety Disorders/drug therapy , Dorsal Raphe Nucleus/metabolism , Galanin/metabolism , Male , Periaqueductal Gray/drug effects , Rats, Wistar , Receptor, Galanin, Type 1/metabolism , Receptor, Galanin, Type 2/metabolism , Serotonin 5-HT1 Receptor Antagonists/pharmacology
2.
Braz. j. med. biol. res ; 45(11): 1025-1030, Nov. 2012. ilus, tab
Article in English | LILACS | ID: lil-650579

ABSTRACT

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.


Subject(s)
Animals , Male , Rats , Anxiety/physiopathology , Behavior, Animal/drug effects , Escape Reaction/drug effects , Panic Disorder/physiopathology , Periaqueductal Gray/drug effects , Behavior, Animal/physiology , Bicuculline/pharmacology , Electrodes, Implanted , Escape Reaction/physiology , Maze Learning/drug effects , Maze Learning/physiology , Periaqueductal Gray/physiology , Rats, Wistar
3.
Braz J Med Biol Res ; 45(11): 1025-30, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22850873

ABSTRACT

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.


Subject(s)
Anxiety/physiopathology , Behavior, Animal/drug effects , Escape Reaction/drug effects , Panic Disorder/physiopathology , Periaqueductal Gray/drug effects , Animals , Behavior, Animal/physiology , Bicuculline/pharmacology , Electrodes, Implanted , Escape Reaction/physiology , Male , Maze Learning/drug effects , Maze Learning/physiology , Periaqueductal Gray/physiology , Rats , Rats, Wistar
4.
Neurobiol Learn Mem ; 81(1): 100-3, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14670364

ABSTRACT

A wealth of evidence indicates that angiotensin II (Ang II) is involved in learning and memory. However, the precise role of this peptide in these cognitive processes is still controversial, with data indicating either an inhibitory or an enhancing action. The present study was designed to further investigate the effects of intracerebroventricular injections of Ang II (0.5, 1 or 3nmol/5microl) on a step-through passive avoidance task in male adult Wistar rats. When administered pretraining, Ang II did not affect the acquisition of passive avoidance, but markedly improved avoidance performance when given before the retrieval test. The latter effect was observed in retest sessions performed up to 72h after training. Administration of the peptide five minutes after training impaired retention of inhibitory avoidance. Therefore, Ang II may exert opposite effects on passive avoidance memory according to its interference with brain mechanisms leading to the storage or retrieval of this aversively motivated task.


Subject(s)
Angiotensin II/pharmacology , Association Learning/drug effects , Avoidance Learning/drug effects , Conditioning, Classical/drug effects , Mental Recall/drug effects , Retention, Psychology/drug effects , Animals , Brain/drug effects , Dose-Response Relationship, Drug , Fear/drug effects , Injections, Intraventricular , Male , Motivation , Motor Activity/drug effects , Rats , Rats, Wistar , Reaction Time/drug effects
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