ABSTRACT: Conditioned cues can elicit relapse to drug- and food-seeking behavior over prolonged periods of abstinence. If seeking behavior depends on mesolimbic dopamine D1 receptors, blocking these receptors should reduce seeking behavior.
We examined the effects of either systemic or intra-nucleus accumbens administration of the D1 antagonist SCH 23390 on extinction responding (sucrose seeking) by rats either 1 or 30 days into forced abstinence.
Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After either 1 or 30 days of forced abstinence, rats received systemic (0, 1, 5, or 25 μg/kg IP) or bilateral nucleus accumbens core or shell (0.3 or 0.6 μg/site) injections of SCH 23390 prior to extinction testing.
Saline-treated rats responded more during extinction following 30 vs. 1 day of forced abstinence ("incubation of craving"). Systemic SCH 23390 reduced sucrose seeking after 1 day of forced abstinence, significantly reducing responding following pretreatment with 1, 5, and 25 μg/kg SCH 23390, but only 25 μg/kg significantly reduced sucrose seeking after 30 days of forced abstinence. SCH 23390 (0.3 or 0.6 μg/site) in the core or shell of the nucleus accumbens reduced sucrose seeking in all groups.
Nucleus accumbens D1 receptors are involved in sucrose seeking, but it is not clear if they are involved in the incubation of craving. The fact that D1 antagonism reduced sucrose seeking across an extended period of abstinence may be of use for development of treatment strategies for relapse.
Psychopharmacologia 02/2011; 216(2):219-33. · 4.08 Impact Factor
ABSTRACT: Responding for a drug- or sucrose-paired cue increases over forced abstinence (incubation of craving). If the incentive value of a cue depends on the incentive value of the primary reward, devaluing the primary reward should reduce cue reactivity.
We investigated whether conditioned taste aversion (CTA) to sucrose would transfer to a sucrose-paired cue after 1 or 30 days of forced abstinence and whether CTA after 1 day of forced abstinence would affect incubation of craving.
Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After 1 (Exp.1) or 30 (Exp.2) days of forced abstinence, rats received two home-cage pairings of sucrose with either LiCl (65 mg/kg, IP) to produce CTA or saline as a control. Two days later, rats responded for the cue alone. The following day, sucrose consumption was assessed in the same operant conditioning chamber. Exp.1 rats were tested again 1 month later to determine if CTA would affect incubation of craving.
Exp.1: CTA after 1 day of forced abstinence did not attenuate cue reactivity when tested immediately after CTA, nor did the treatment affect incubation of craving or incubation of sucrose consumption. Exp.2: CTA after 1 month of forced abstinence resulted in a significant reduction in cue reactivity.
The incentive values of sucrose and the conditioned representation of sucrose increase over an extended period of forced abstinence. This incubation appears to facilitate the transfer of an aversion to the primary reward to the conditioned cue.
Psychopharmacologia 03/2010; 208(4):521-30. · 4.08 Impact Factor
ABSTRACT: This study examined the effect of environmental enrichment on sucrose seeking in rats made abstinent from sucrose for 1 month, as measured by response for a tone+light cue previously associated with 10% sucrose self-administration. Rats were either enriched throughout the study (experiment 1) or only after sucrose self-administration training (experiment 2). Enrichment consisted of either housing the rats in pairs or grouping four rats (ENR4) in a large environment, both with novel objects. Controls (CON) were singly housed without novel objects. In experiment 1, ENR4 rats responded less to the sucrose-paired cue versus CON rats, but this difference was not statistically significant. In contrast, the decrease in response of ENR4 rats versus CON rats in experiment 2 was dramatic and significant. These findings, along with findings from other laboratories, support a hypothesis that the enrichment may provide individuals with a greater ability to discriminate the availability of reward. This may impart a decreased vulnerability to relapse behavior. Therefore, these results are relevant to both eating disorder and drug addiction - disorders characterized by relapse.
Behavioural pharmacology 01/2009; 19(8):777-85. · 2.85 Impact Factor