Basolateral amygdala activity during the retrieval of associative learning under anesthesia.

Associative learning can occur under anesthesia and its neural correlates have begun to be elucidated. During discrimination learning under anesthesia in rats, lateral amygdala excitability increases in response to a conditioned stimulus (CS+) previously paired with electrical stimulation of the paw but not to another stimulus presented alone (CS-). Similarly, medial prefrontal cortex activity increases selectively during CS+ presentation after discrimination learning but this occurs only in neurons receiving input from the basolateral amygdala (BLA), the main source of amygdaloid projections to this region. However, BLA activity during discrimination learning under anesthesia has not been investigated. Here we used in vivo electrophysiology to examine BLA activity before and after associative learning and during later memory retrieval in anesthetized rats. We examined extracellular unit and local field potential (LFP) activity using an auditory discrimination learning paradigm. Rats were repeatedly presented with two distinct sounds, one of which was paired with electrical stimulation of the paw. One hour later, the paired sound (CS+) was presented alone along with the sound not paired with electrical stimulation (CS-). We found increased unit firing late (1 h) but not early (5 min) after learning. LFP power was increased both early and late after learning. In control experiments we also found increased unit and LFP activity late after electrical stimulation alone. After discrimination learning, unit firing increased in response to CS+, but not CS-, presentation. LFP power also showed a modest increase during CS+, compared to CS-, presentation. These findings suggest that discrimination learning under anesthesia can occur at the neural level in BLA. The potential relevance of these results is discussed in relation to previous studies examining neural activity during fear learning and memory processing in conscious animals.

Impact of regional 5-HT depletion on the cognitive enhancing effects of a typical 5-ht(6) receptor antagonist, Ro 04-6790, in the Novel Object Discrimination task.

RATIONALE: Selective 5-ht(6) receptor antagonists like Ro 04-6790 prolong memory in many rodent preclinical paradigms, possibly by blocking tonic 5-HT-evoked GABA release and allowing disinhibition of cortico-limbic glutamatergic and cholinergic neurones. If this is the case, behavioural responses to Ro 04-6790 should be abolished by depletion of endogenous 5-HT, and selective lesions of dorsal raphé (DR) or median raphé (MR) 5-HT pathways would allow the neuroanatomical substrates underlying the cognitive effects of 5-ht(6) receptor antagonists to be elucidated. OBJECTIVES: This study compared the effect of Ro 04-6790 on novel object discrimination (NOD) before and after sham or 5,7-dihydroxytryptamine (5,7-DHT)-induced lesions produced by injection into the lateral ventricles (LV), DR or MR. MATERIALS AND METHODS: NOD tests used a 4 h inter-trial interval (ITI) and Ro 04-6790 (10 mg kg(-1) i.p.) was administered 20 min before the familiarization trial. Brain region-specific 5-HT depletion was assessed by high performance liquid chromatography with electrochemical detection (HPLC-ED). RESULTS: Widespread LV or selective MR, but not DR lesions, abolished the ability of Ro 04-6790 to delay natural forgetting. Successful performance of all lesioned rats in subsequent 'drug-free' NOD tests using a 1 h ITI excluded the possibility of any confounding effects on visual acuity or motivation. CONCLUSIONS: The ability of Ro 04-6790 to prolong object recognition memory requires blockade of MR 5-HT function. Because DR lesions did not produce the expected depletion of striatal 5-HT an additional contribution of DR inputs to this region cannot be completely excluded.

Effects of chronic infusion of neurotensin and a neurotensin NT1 selective analogue PD149163 on amphetamine-induced hyperlocomotion.

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.