Effects of nicotine and a cannabinoid receptor agonist on negative contrast: distinction between anxiety and disappointment?
BACKGROUND
Animals trained to lick for a sucrose solution of a given incentive value that subsequently encounter an incentive downshift (i.e. 32-4% sucrose) display an exaggerated decrease in the amount consumed, relative to unshifted controls. This change has been classified as a successive negative contrast (SNC) effect. The emotional component to this robust behavioural change is dynamic and changes from post-shift day (PSD) 1 to 2. Anxiolytics block SNC, but the possible link between anxiety and SNC needs further exploration. Both nicotine and a cannabinoid receptor agonist have been reported to change anxiety and both have actions on the reward process, but their effects on SNC have not been investigated.


OBJECTIVE
To determine: (1) whether exposure to SNC evokes an anxiogenic response; (2) whether an anxiolytic dose of nicotine has the same effects on SNC as those of chlordiazepoxide; (3) the effects of a low (anxiolytic) and a high (anxiogenic) dose of the cannabinoid receptor agonist CP 55,940 on SNC.


METHODS
Two groups of animals were given access to high (32%) or low (4%) sucrose solutions for 5 min per day for 10 days. On PSD 1 and 2, the shifted group had access to a devalued incentive (from 32 to 4% sucrose) and the unshifted group remained at 4% sucrose. The volumes (ml) of sucrose solution consumed were measured pre-shift and on PSD 1 and 2. In experiment 1, immediately after SNC testing on PSD 1 and 2, the rats were tested in the social interaction and elevated plus-maze tests of anxiety. In experiment 2, the effects of chlordiazepoxide (5 and 7.5 mg/kg) and nicotine (0.1 mg/kg) were examined on PSD 1 and 2. In experiment 3, the effects of CP 55,940 (5 and 40 microg/kg) were examined on PSD 1 and 2.


RESULTS
There were no anxiogenic effects of shift in either test of anxiety on either test day. However, on PSD 1, the shifted group had significantly higher locomotor activity and spent a higher percentage of time on the open arms, perhaps reflecting search strategies. Nicotine was without significant effect on SNC on either test day. On PSD 1, chlordiazepoxide (5 mg/kg) and CP 55,940 (5 and 40 microg/kg, IP) blocked SNC. On PSD 2, both doses of chlordiazepoxide and the low, anxiolytic dose of CP 55,940 (5 microg/kg) blocked SNC, the high dose of CP 55,940 was without effect.


CONCLUSIONS
The pattern of results allows for the separation between effects on anxiety and SNC. The block of contrast on PSD 1 was independent of changes in anxiety, since both anxiolytic and anxiogenic drug doses were effective. It is suggested that this may provide an animal model of disappointment in which the cannabinoid system plays an important role. An anxiolytic action would seem to be a necessary, but not a sufficient, action to block SNC on PSD 2.
Genn
Rachel F
RF
Psychopharmacology Research Unit, Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, London, SE1 1UL, UK. r.genn@iop.kcl.ac.uk
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D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D003511:Cyclohexanols / Q000494:pharmacology; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D043882:Receptors, Cannabinoid / Q000502:physiology
D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D009538:Nicotine; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol