Social defeat stress sensitization and intravenous cocaine self administration
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Social defeat stress, sensitization, and intravenous cocaine self-administration. By Jasmine Yap and Klaus Miczek. Behavior sensitization is proposed to be very important in compulsive drug use and many psychotic disorders

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Social defeat stress sensitization and intravenous cocaine self administration

Social defeat stress, sensitization, and intravenous cocaine self-administration

By Jasmine Yap and Klaus Miczek




  • Process of sensitization addiction

    • Repeated, intermittent administration leads to progressively increased ( or sensitized) locomotor response

    • Important in transition from recreational to compulsive drug addicts



  • Social defeat modulates changes in: increased dopamine levels in the nucleus accumbens (up to 65%) and in other mesocorticolimbic regions such as the prefrontal cortex

    • circadian rhythmicity,

    • long lasting neural adaptations in immediate early gene expression,

    • induces cross-sensitization to psychostimulants

    • Decrease in cell proliferation in dentate gyrus



Methods materials
Methods & Materials effects on mesocorticolimbic dopamine systems

  • Adult male CFW mice

    • 55 to 60 days old

    • 25 g

    • On 12 hour light/dark cycle


  • Intruder mice effects on mesocorticolimbic dopamine systems

    • Housed individually in clear cages

      • 28cm x 17cm x 14cm3

  • Resident mice

    • Housed in pairs with a female for 3 weeks

      • Facilitates display of aggression

      • Insures resident always wins confrontation


  • Amphetamine sensitization: effects on mesocorticolimbic dopamine systems

    • Intraperitoneal injections with D-amphetamine sulfate or saline for 10 days

    • Locomotion assessed on days 1,4,7,10 for 15 min. before and 30 min after injection

    • Expression of sensitization tested on day 20

      • Locomotor activity assessed


  • Social defeat stress ( 10 days) effects on mesocorticolimbic dopamine systems

    • Injected with saline

    • Subjected to social defeat

      • Broken into 3 phases

        • Instigation

        • Defeat

        • Threat


  • Instigation effects on mesocorticolimbic dopamine systems

    • Intruder placed in protective cage with perforated walls in resident’s cage for 5 min

      • Unrestricted auditory, olfactory, and visual contact

  • Defeat

    • Intruder placed in cage unprotected

    • Allowed to be attacked until assumes defeat posture and held for 3 sec.


Defeat posture
Defeat Posture effects on mesocorticolimbic dopamine systems


  • Threat phase effects on mesocorticolimbic dopamine systems

    • Intruder is placed in resident cage in a protective cage for 5 additional min


  • 10 days after last encounter effects on mesocorticolimbic dopamine systems

    • Given saline injection and locomotor activity assessed for 20 min

    • Then given either cumulative doses of amphetamines of 1.0, 1.8, and 3.0 mg/kg and locomotor activity was assessed for 20 min

    • Or single amphetamine doses of 1.0, 1.5, 2.0, or 2.5 mg/kg and activity assessed for 45 min




  • Nose-poke amphetamines

    • 1 day after amphetamine challenge

    • Conditioned to nose-poke an illuminated hole for food

    • 5 days

    • Implanted with jugular catheter


  • 5 days post surgery amphetamines

    • Acquisition phase for 5 days

      • Received 1 mg/kg infusion of cocaine on a fixed ratio 2 schedule

  • Then allowed to self administer daily for 3 hrs or until 50 infusions


  • Socially defeated mice amphetamines

    • Start acquisition phase of cocaine self-administration on day 20 for 5 days

    • Self administration begins during period of cross-sensitization to psychostimulants


  • After acquisition phase amphetamines

    • Begin progressive ratio sessions of 0.3 mg/kg per infusion for 3 days to determine the breaking point

    • Between sessions allowed to self-administer 1.0 mg/kg for 3 hrs a day to prevent extinction


Results
Results amphetamines














  • Map defeat stress-induced sensitization


  • Rats with previous social defeats defeat stress-induced sensitization

    • Exposure to olfactory, visual, and auditory cues increase dopamine release and acquire cocaine seeking behavior in half the time of non-stressed animals


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