Amphetamine can increase conditioning to poor predictors of reinforcement in selective learning tasks (e.g. latent inhibition, LI). In the present study, a noise stimulus was contiguous with footshock or presented at a trace interval. A flashing light background stimulus was used to measure contextual conditioning. Experiment 1 used 1.5 mg/kg and 6 mg/kg dl-amphetamine. Experiments 2 and 3 used 0.5 mg/kg and 1.5 mg/kg d-amphetamine. Unconditioned stimuli parameters (intensity, number, duration) were also manipulated from one experiment to the next. Amphetamine consistently increased conditioning to the background stimulus, and increased conditioning to the trace stimulus at higher footshock intensity (Experiment 3). Thus, amphetamine increased conditioning only to relatively uninformative predictors. The effect on conditioning to trace conditioned stimuli depended on the level of reinforcer but increased conditioning to background did not. Throughout, there was no effect of amphetamine on conditioning of the contiguous stimulus. Thus, the results did not simply arise because amphetamine increased conditioning under any condition in which conditioning without amphetamine was poor. The results are discussed in terms of amphetamine effects on breadth of attention and LI to context.
Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.
There is evidence to suggest that neurotensin (NT) may enhance cognitive function. The present study, therefore, examined the role of NT in associative learning between a conditioned stimulus (CS) and an unconditioned stimulus (UCS). This was tested in a trace procedure using conditioned suppression of drinking with a noise CS and foot shock UCS. We compared the effects of an NT agonist (PD 149163, 0.25 and 1 mg/kg) with those of an NT antagonist (SR 142948A, 0.01 and 0.1 mg/kg). Conditioning after drug treatment was followed by drug-free tests of associative learning. At 0.25 but not 1 mg/kg, PD 149163 selectively increased conditioning over the trace interval: there was no such increased conditioning in the 0s group. This increased conditioning over the trace is an effect that is reliably produced by dopamine (DA) agonists in the same procedure. However, dissimilar to the effects of DA agonists, conditioning to box context, was reduced under PD 149163. Doses of SR 142948A, selected on the basis of their effects in similar aversively motivated tests of latent inhibition, were without intrinsic effect in the present procedure. The dose-related dissociation between trace and contextual conditioning effects under PD 149163 is considered as cognitive enhancement.
The effects of amphetamine on selective learning were tested in a trace conditioning procedure, in which the informativeness of the conditioned stimulus (CS) (noise) was manipulated through the introduction of a time interval before the delivery of the unconditioned stimulus (UCS) (food). The results showed that d-amphetamine (0.5 and 1.5 mg/kg) impaired both the expression (Experiment 1b) and acquisition (Experiment 2) of appetitive conditioning. This was true for both trace and contiguously conditioned groups. The effects of the 0.5 mg/kg dose of d-amphetamine were not attributable to general motor (measured pre-CS) or motivational (measured post-UCS) effects of the drug. Moreover, the same pattern of effects (impaired appetitive conditioning, irrespective of the trace interval between CS and UCS) was confirmed in drug-free extinction tests. By contrast to the general depression in the acquisition and expression of associative learning observed under amphetamine, the 0.5 mg/kg dose promoted the acquisition of anticipatory responses made later in the trace interval (in Experiment 2 but, again, not the expression of previous conditioning in Experiment 1b). This suggests a dissociable effect of low-dose d-amphetamine on learning about the temporal relationship between CS and UCS.
Neurotensin (NT) has been proposed as an endogenous antipsychotic based in part on the similarity in behavioural effects to antipsychotic drugs, for example, attenuation of both amphetamine-induced hyperlocomotion (AH) and amphetamine disrupted pre-pulse inhibition in the rat. However, there is some evidence that repeated administration of NT or an analogue produces behavioural tolerance to such effects. The present experiments sought to confirm and extend these findings by testing the effects on AH of 7 days central administration of NT and the NT1 selective analogue PD 149163 and the effects of 21 days central administration of NT. NT and PD149163 continuously administered for 7 days produced no effect on AH (in contrast to attenuation with a single injection here and previously reported), whereas 21 days of NT administration potentiated AH. Together, these studies report that the effects of NT or a NT analogue on AH depends on the duration of administration of peptide. The results are discussed in comparison with the reported antipsychotic properties of acute administration of NT and possible mechanisms involving NT1 receptors.
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