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Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: : Ketamine is a general anesthetic (GA) that activates several neurotransmitter pathways in various part of the brain. The acute effects as GA are the most well-known and sought-after: to induce loss of responsiveness and to produce immobility during invasive procedures. However, there is a concern that repeated exposure might induce behavioral changes that could outlast their acute effect. Most research in this field describes how GA affects cognition and memory. Our work is to access if general anesthesia with ketamine can disrupt the motivational behavior trait, more specifically measuring impulsive behavior.

Methods: : Aiming to evaluate the effects of exposure to repeat anesthetic procedures with ketamine in motivational behavior, we tested animals in a paradigm of impulsive behavior, the variable delay-to-signal (VDS). In addition, accumbal and striatal medium spiny neurons morphology was assessed.

Results: : Our results demonstrated that previous exposure to ketamine deep-anesthesia affects inhibitory control (impulsive behavior). Specifically, ketamine exposed animals maintain a subnormal impulsive rate in the initial periods of the delays. However, in longer delays while control animals progressively refrain their premature unrewarded actions, ketamine-exposed animals show a different profile of response with higher premature unrewarded actions in the last seconds. Animals exposed to multiple ketamine anesthesia also failed to show an increase in premature unrewarded actions between the initial and final periods of 3 s delays. These behavioral alterations are paralleled by an increase in dendritic length of medium spiny neurons of the nucleus accumbens (NAc).

Conclusions: : This demonstrates that ketamine anesthesia acutely affects impulsive behavior. Interestingly, it also opens up the prospect of using ketamine as an agent with the ability to modulate impulsivity trait.

No MeSH data available.


Related in: MedlinePlus

General organization of the experiment and operational diagrams of the VDS and preceding training protocol. The VDS consisted in two parts: the training protocol (10 sessions) and the VDS proper (1 session); while in the first the delay-to-signal was fixed (3 s) and pre-signal nose pokes were punished (TO), in the VDS proper, 2 blocks of 25 trials at 3 s delay were interposed by a block of 70 trials at 6 s and 12 s, pre-signal responses were registered but not punished with a TO. In both training and VDS the signal duration was set to a maximum of 60 s; the absence of a response within this period was registered as an omission. TO, timeout; VDS, variable delay-to-signal task.
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Figure 1: General organization of the experiment and operational diagrams of the VDS and preceding training protocol. The VDS consisted in two parts: the training protocol (10 sessions) and the VDS proper (1 session); while in the first the delay-to-signal was fixed (3 s) and pre-signal nose pokes were punished (TO), in the VDS proper, 2 blocks of 25 trials at 3 s delay were interposed by a block of 70 trials at 6 s and 12 s, pre-signal responses were registered but not punished with a TO. In both training and VDS the signal duration was set to a maximum of 60 s; the absence of a response within this period was registered as an omission. TO, timeout; VDS, variable delay-to-signal task.

Mentions: The anesthetic procedure was performed through intra-peritoneal injections of ketamine according to the following scheme: an initial anesthetic dose of 100 mg/Kg of ketamine to induce anesthesia and then two subsequent injections of 50 mg/Kg. Anesthetized animals were placed over a warming pad with feedback control at 37°C in order to maintain body temperature. Anesthesia was considered adequate when animals lost the righting reflex and were irresponsive to tail pinch. The following dosage (50 mg/ml) was given when animals regain response to pressure stimuli in the tail. The anesthesia protocol was applied between the end of the training sessions and before the VDS test session (see below) in three GA procedures. Average time of anesthesia was 2.5 h. A washout period of at least 12 h was applied between the last anesthetic procedure and the initiation of the VDS protocol (see Figure 1).


Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior
General organization of the experiment and operational diagrams of the VDS and preceding training protocol. The VDS consisted in two parts: the training protocol (10 sessions) and the VDS proper (1 session); while in the first the delay-to-signal was fixed (3 s) and pre-signal nose pokes were punished (TO), in the VDS proper, 2 blocks of 25 trials at 3 s delay were interposed by a block of 70 trials at 6 s and 12 s, pre-signal responses were registered but not punished with a TO. In both training and VDS the signal duration was set to a maximum of 60 s; the absence of a response within this period was registered as an omission. TO, timeout; VDS, variable delay-to-signal task.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121127&req=5

Figure 1: General organization of the experiment and operational diagrams of the VDS and preceding training protocol. The VDS consisted in two parts: the training protocol (10 sessions) and the VDS proper (1 session); while in the first the delay-to-signal was fixed (3 s) and pre-signal nose pokes were punished (TO), in the VDS proper, 2 blocks of 25 trials at 3 s delay were interposed by a block of 70 trials at 6 s and 12 s, pre-signal responses were registered but not punished with a TO. In both training and VDS the signal duration was set to a maximum of 60 s; the absence of a response within this period was registered as an omission. TO, timeout; VDS, variable delay-to-signal task.
Mentions: The anesthetic procedure was performed through intra-peritoneal injections of ketamine according to the following scheme: an initial anesthetic dose of 100 mg/Kg of ketamine to induce anesthesia and then two subsequent injections of 50 mg/Kg. Anesthetized animals were placed over a warming pad with feedback control at 37°C in order to maintain body temperature. Anesthesia was considered adequate when animals lost the righting reflex and were irresponsive to tail pinch. The following dosage (50 mg/ml) was given when animals regain response to pressure stimuli in the tail. The anesthesia protocol was applied between the end of the training sessions and before the VDS test session (see below) in three GA procedures. Average time of anesthesia was 2.5 h. A washout period of at least 12 h was applied between the last anesthetic procedure and the initiation of the VDS protocol (see Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: : Ketamine is a general anesthetic (GA) that activates several neurotransmitter pathways in various part of the brain. The acute effects as GA are the most well-known and sought-after: to induce loss of responsiveness and to produce immobility during invasive procedures. However, there is a concern that repeated exposure might induce behavioral changes that could outlast their acute effect. Most research in this field describes how GA affects cognition and memory. Our work is to access if general anesthesia with ketamine can disrupt the motivational behavior trait, more specifically measuring impulsive behavior.

Methods: : Aiming to evaluate the effects of exposure to repeat anesthetic procedures with ketamine in motivational behavior, we tested animals in a paradigm of impulsive behavior, the variable delay-to-signal (VDS). In addition, accumbal and striatal medium spiny neurons morphology was assessed.

Results: : Our results demonstrated that previous exposure to ketamine deep-anesthesia affects inhibitory control (impulsive behavior). Specifically, ketamine exposed animals maintain a subnormal impulsive rate in the initial periods of the delays. However, in longer delays while control animals progressively refrain their premature unrewarded actions, ketamine-exposed animals show a different profile of response with higher premature unrewarded actions in the last seconds. Animals exposed to multiple ketamine anesthesia also failed to show an increase in premature unrewarded actions between the initial and final periods of 3 s delays. These behavioral alterations are paralleled by an increase in dendritic length of medium spiny neurons of the nucleus accumbens (NAc).

Conclusions: : This demonstrates that ketamine anesthesia acutely affects impulsive behavior. Interestingly, it also opens up the prospect of using ketamine as an agent with the ability to modulate impulsivity trait.

No MeSH data available.


Related in: MedlinePlus