AIMS: Recent studies suggest that cannabinoid
receptor agonists may promote relapse to drug-seeking behaviour
after a period of abstinence. In this study, the ability of
Delta(9)-tetrahydrocannabinol (THC) to reinstate previously
reinforced responding for alcoholic and non-alcoholic beverages
was assessed in rats using a novel lick-based paradigm.
METHODS: Rats were initially given free access
to beer (containing 4.5% ethanol v/v), near-beer (a beverage
that looks and tastes like beer but contains <0.5% ethanol
v/v) or isocaloric sucrose in their home cages for 3 weeks.
They were then trained to lick at a tube to self-administer
the pre-exposed beverage in operant chambers under a VR10 schedule
in 30-min sessions daily. After approximately 3 weeks of such
access, the rats underwent an extinction procedure, so that
licking at the tube produced no reward. Once responding had
ceased, the rats were subjected to various reinstatement tests.
RESULTS: In Experiment 1, the cannabinoid
receptor agonist Delta(9)-THC (1 mg/kg) significantly reinstated
responding, previously reinforced with beer or near-beer. The
effect was unlikely to be caused by increased appetite because
24 h food-deprivation had no such effect. Exposure to cat odour
in the test chamber failed to reinstate responding for beer
or near-beer and caused a complete inhibition of responding.
In Experiment 2, Delta(9)-THC (0.3 and 1 but not 3 mg/kg) again
reinstated beer-seeking behaviour while the 1 mg/kg dose also
reinstated responding in sucrose trained animals. Midazolam
(0.15 mg/kg but not 0.5 or 1.5 mg/kg) produced a modest reinstatement
of beer-seeking but had no effect on sucrose-seeking behaviour.
CONCLUSIONS: The finding that Delta(9)-THC
can reinstate alcohol-seeking provides the impetus for further
research into the involvement of the cannabinoid system in alcohol
craving. However, the reinstatement of near-beer and sucrose-seeking
behaviour caused by Delta(9)-THC suggests a relatively non-specific
effect. This may perhaps be related to the stressor-like effects
of cannabinoids, and their ability to activate key neural circuitry
in the amygdala and bed nucleus of the stria terminalis.