Reduced dopamine function within the medial shell of the nucleus accumbens enhances latent inhibition.

Latent inhibition (LI) manifests as poorer conditioning to a CS that has previously been presented without consequence. There is some evidence that LI can be potentiated by reduced mesoaccumbal dopamine (DA) function but the locus within the nucleus accumbens of this effect is as yet not firmly established. Experiment 1 tested whether 6-hydroxydopamine (6-OHDA)-induced lesions of DA terminals within the core and medial shell subregions of the nucleus accumbens (NAc) would enhance LI under conditions that normally disrupt LI in controls (weak pre-exposure). LI was measured in a thirst motivated conditioned emotional response procedure with 10 pre-exposures (to a noise CS) and 2 conditioning trials. The vehicle-injected and core-lesioned animals did not show LI and conditioned to the pre-exposed CS at comparable levels to the non-pre-exposed controls. 6-OHDA lesions to the medial shell, however, produced potentiation of LI, demonstrated across two extinction tests. In a subsequent experiment, haloperidol microinjected into the medial shell prior to conditioning similarly enhanced LI. These results underscore the dissociable roles of core and shell subregions of the NAc in mediating the expression of LI and indicate that reduced DA function within the medial shell leads to enhanced LI.

Amphetamine effects in appetitive acquisition depend on the modality of the stimulus rather than its relative validity.

Amphetamine has been shown previously to increase the apportioning of associative strength to weak predictors in appetitive Pavlovian conditioning procedures such as latent inhibition and overshadowing. Manipulating the likelihood with which different conditioned stimuli (CSs) predict subsequent delivery of an unconditioned stimulus (UCS) is an alternative method by which the associability of CSs can be influenced. The present experiment tested effects of D-amphetamine (0.5 mg/kg or 1.5 mg/kg administered 15 min prior to conditioning) in appetitive acquisition under partial versus continuous reinforcement of alternative CSs with sucrose pellet UCS delivery. Specifically, male Wistar rats were conditioned to light and tone CSs that were followed by the UCS on 100% or 50% of trials in a cross-over design. It was predicted that amphetamine would disrupt rats' ability to select appropriately the most valid CSs for learning which would be expressed as increased conditioning to weaker, 50% valid CSs. Contrary to prediction, differential responding based on relative validity was preserved under amphetamine, for both light and tone stimuli. Instead, the results showed that responding to light CSs was generally reduced under amphetamine. Conditioning to tone CSs was higher and unaffected by amphetamine. Thus, results demonstrate that amphetamine effects are determined by the properties of the CS used for learning.

Appetitive overshadowing is disrupted by systemic amphetamine but not by electrolytic lesions to the nucleus accumbens shell.

There is evidence that the indirect dopamine (DA) agonist amphetamine (AMP) can disrupt selective learning in an aversive overshadowing task, consistent with a role for the DA system in this form of salience manipulation. In the following experiments we assessed in the male Wistar rat: (1) whether amphetamine disruption of overshadowing extends to an appetitively motivated overshadowing task; and (2) whether selective electrolytic lesions to the n.acc (shell versus core subfields) disrupt appetitively motivated overshadowing. The experiments used sucrose reward pellets as the unconditioned stimulus (UCS). In each case, a conditioned stimulus (CS, light) was either conditioned alone or in compound together with a more intense CS (noise or tone). The presence of overshadowing was demonstrated as reduced conditioning to the light when it had been previously conditioned in compound compared to when it had been conditioned alone. It was predicted that AMP and lesions to the n.acc shell would disrupt overshadowing. AMP was found to abolish overshadowing at 0.5 mg/kg, but not at 1 mg/kg. Contrary to prediction, the shell lesioned animals did not differ from shams. The results of Experiment 1 add to the evidence that the DA system can moderate salience processing of weaker predictors, also in cases where CS salience is manipulated directly via the physical intensities of the stimuli, as here. However, in terms of the brain structures involved, Experiment 2 suggests that, overshadowing is moderated by projections of the DA system without n.acc.

Methylphenidate and nicotine focus responding to an informative discrete CS over successive sessions of appetitive conditioning.

Methylphenidate (MP) and nicotine would be expected to improve associative learning, though previous evidence suggests that they should reduce the selectivity with which associations are formed. Here we tested their effects on learning the association between a conditioned stimulus (CS) and food (unconditioned stimulus, UCS) in male Wistar rats. The UCS was delivered immediately (0 s) following CS offset or after a 10 s trace. In addition to the measures of discrete CS conditioning, contextual and trace responding was measured in the inter-trial- and the inter-stimulus-interval, respectively. In all cases, conditioning was measured as nose poking for food. Both MP and nicotine improved the acquisition of discrete cue conditioning. Acquisition was accelerated (compared to saline) under 5 but not 1 mg/kg MP and 0.6, but not 0.4 mg/kg nicotine. In each case, this effect was observed in 0 s but not 10 s conditioned groups. For comparison, some earlier published data obtained following the same procedure with D-amphetamine were re-analysed in the same way. Amphetamine similarly improved conditioning in the 0 s group, in this case at 0.5, but not 1.5 mg/kg. Thus three different dopamine agonists increased the ability to focus responding to CS presentations over successive sessions of appetitive acquisition.

Lesions of the nucleus accumbens shell can reduce activity in the elevated plus-maze.

Across different behavioural tasks, nucleus accumbens (n.acc) lesions have generated conflicting effects on locomotor activity and in particular, the relative roles of the n.acc shell and core subfields in this have been controversial. To date there is only one study examining effects of lesions to the medial n.acc on elevated plus-maze (EPM) behaviour; these lesions were shown to increase both locomotor and exploratory activity. Given the well-documented distinction between shell and core, the present study sought to extend previous research by testing lesions selective to each n.acc subfield in the EPM. Results showed no statistical differences between core lesioned and sham-operated animals on any measure. In contrast, shell lesions consistently reduced locomotion and exploratory activity. This direction of effects is opposite to that previously observed after medial n.acc. lesions. In conclusion, locomotion and exploratory activity were clearly reduced by shell but not core lesions, consistent with other evidence for the functional heterogeneity of n.acc shell and core.

Methylphenidate can reduce selectivity in associative learning in an aversive trace conditioning task.

There are good grounds to expect that methylphenidate (MP) should enhance cognitive function. However, experimental evidence on this point is scant. The present study therefore examined the effects of MP on learning the association between a conditioned stimulus (CS, in this case, noise) and an unconditioned stimulus (UCS, in this case, footshock) in an aversive variant of a trace conditioning procedure. Learning was measured off-the-baseline as conditioned suppression of drinking (both latencies to drink, expressed as suppression ratios, and the amount drunk, expressed as the number of licks, in the presence of the CS). In addition to the measures of discrete cue conditioning, MP effects on contextual conditioning were measured as suppression to apparatus cues and an experimental background stimulus. MP was administered at 1 or 5 mg/kg prior to conditioning sessions. As attention deficit hyperactivity disorder (ADHD) has been characterized as involving a ;wide attentional window' (e.g. Shalev and Tsal, 2003), it was predicted that MP, as the treatment of choice for ADHD, should increase selectivity (narrowing the attentional window). This outcome would show as reduced levels of conditioning (compared to control rats) to less informative trace and contextual cues present during conditioning. Contrary to prediction, both 1 and 5 mg/kg MP increased learning about all the available stimuli, including the less informative trace CS and the background stimulus. These findings are consistent with reduced rather than increased selectivity in learning (because of increased rather than decreased conditioning to weak cues) under MP.

Electrolytic lesions to nucleus accumbens core and shell have dissociable effects on conditioning to discrete and contextual cues in aversive and appetitive procedures respectively.

The nucleus accumbens (n. acc.) has been implicated in conditioning to both discrete and contextual cues but its precise role is as yet controversial because conflicting patterns of effect have been reported. These inconsistencies may relate to the extent to which the lesions used encroach on different subfields of n. acc. and the use of different task variants. The present study compared the effects of selective lesions of shell and core subfields of nucleus accumbens (n. acc.) across aversive and appetitive trace conditioning variants. In both experiments, an auditory stimulus was contiguous with footshock or food, or presented at a trace interval. A continuous flashing light in each case provided an experimental background stimulus. Conditioning to the cues provided by the experimental chambers was also assessed. Rats with electrolytic lesions to the n. acc. shell and core showed different patterns of effect in aversive (Experiment 1) and appetitive (Experiment 2) variants of this procedure. In Experiment 1, the core lesion reduced the difference between trace and contiguously conditioned groups, in responding to the discrete noise stimulus. However, neither lesion had any detectable effect on contextual conditioning. In Experiment 2, the shell lesion clearly increased contextual conditioning, selectively in the trace conditioned group, but neither lesion had any detectable effect on discrete cue conditioning. Thus, whilst the shell and core lesions produced dissociable effects on discrete cue and contextual conditioning, the conclusions to be drawn depend on the procedural variant in use.