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Different hippocampal molecular requirements for short- and long-term retrieval of one-trial avoidance learning.

Rats were trained in one-trial step-down inhibitory avoidance and tested either 3 h or 31 days later. Ten minutes prior to the retention test, through indwelling cannulae placed in the CA1 region of the dorsal hippocampus, they received 0.5 microl infusions of: saline, a vehicle (2% dimethylsulfoxide in saline), the glutamate NMDA receptor blocker, aminophosphonopentanoic acid (AP5) (5.0 microg), the AMPA/kainate receptor blocker, cyanonitroquinoxaline dione (CNQX) (0.25 or 1.25 microg), the metabotropic receptor antagonist, methylcarboxyphenylglycine (MCPG) (0.5 or 2.5 microg), the inhibitor of calcium/calmodulin-dependent protein kinase II (KN62) (3.5 microg), the inhibitor of cAMP-dependent protein kinase (PKA), Rp-cAMPs (0.1 or 0.5 microg), the stimulant of the same enzyme, Sp-cAMPs (0.1 or 0.5 microg), or the inhibitor of the mitogen-activated protein kinase (MAPK) kinase, PD098059 (10 or 50 microM). CNQX, KN62 and PD098059 were dissolved in the vehicle; the other drugs were dissolved in saline. All these drugs, at the same doses, had been previously found to affect short- and long-term memory formation of this task. Retrieval measured 3 h after training (short-term memory) was blocked by CNQX and MCPG, and was unaffected by all the other drugs. In contrast, retrieval measured at 31 days was blocked by MCPG, Rp-cAMPs and PD098059, enhanced by Sp-cAMPs, and unaffected by CNQX, AP5 or KN62. The results indicate that, in CA1, glutamate metabotropic receptors are necessary for the retrieval of both short- and long-term memory; AMPA/kainate receptors are necessary for short-term but not long-term memory retrieval, and NMDA receptors are uninvolved in retrieval. Both the PKA and MAPK signalling pathways are required for the retrieval of long-term but not short-term memory.

Animals↗

Spontaneous and artificial lesions of magnocellular reticular formation of brainstem deteriorate avoidance learning in senescence-accelerated mouse SAM.

The role of the magnocellular reticular formation (MGRF) of the brainstem on learning and memory was examined in memory-deficient mice with spontaneous spongy degeneration in the brainstem (senescence-accelerated mouse, SAMP8) and control mice (accelerated-senescence resistant mouse, SAMR 1). SAMP8 showed spontaneous age-related impairment of learning and memory, as determined by passive and active avoidance responses. The deficits of learning and memory function in passive avoidance performances began at two months of age and increased with ageing. In the brains of SAMP8 at one month of age and older, spongy degeneration was mainly observed in the brainstem, while no vacuoles were evident in SAMR1 control (normal ageing mouse) brains in the age range tested (up to 12 months). The vacuolization in SAMP8 was marked in the MGRF, especially in the dorsomedial MGRF. Quantitative analysis of the vacuolization showed that the total area and number of vacuoles in the MGRF increased with age, and they were affected by the degree of deficits in learning and memory. The latency 24 h after footshock in passive avoidance tests decreased with the increase in total area and number of vacuoles in MGRF. The number of shocks in active avoidance tests increased with the increase in total number and area of vacuoles. Thus, learning and memory ability in passive and active avoidance responses deteriorated with enlargement in the vacuolated area in MGRF, and it was assumed that MGRF (especially, the dorsomedial part) possesses functions related to learning and memory. To confirm this notion, behavior and memory tests (passive avoidance and active avoidance tests, open field tests and shock sensitivity measurements) were carried out in SAMR1 mice, whose bilateral dorsomedial MGRF was destroyed electrolytically (MGRF-lesioned mice). The MGRF-lesioned mice showed no difference from sham mice in sensory threshold or open field activity; however, there was severe deterioration in passive avoidance behavior and impairment in the active avoidance performances. From the results in SAMP8 and MGRF-lesioned mice, it was confirmed that MGRF (especially the dorsomedial part) has functions related to learning and memory, and is one part in the learning and memory system of the brain. Thus, SAMP8 can serve as a model of RF-lesioned mice with impaired learning and memory functions.

Aging↗

Effect of selective muscarinic receptor agonists and antagonists on active-avoidance learning acquisition in rats.

Effect of some selective muscarinic receptor agonists and antagonists was investigated on learning acquisition in an active-avoidance paradigm in rats which records an anticipatory conditioned avoidance apart from the classical conditioned avoidance response. The muscarinic M1 agonists, arecholine, pilocarpine and McN-A-343, facilitated learning acquisition, which was attenuated by the selective M1 antagonist, pirenzepine. On the other hand, M2 receptor agonist, carbachol, and physostigmine, induced a dose-related dual response, with lower doses retarding and higher doses facilitating the learning acquisition. The former effect was attenuated by gallamine, a muscarinic M2 antagonist, while the latter response was inhibited by pirenzepine, indicating that these putative M2 receptor agonist lose their receptor specificity on dose increment. The selective M2 receptor antagonists, gallamine and AF-DX 116, facilitated learning acquisition, which was inhibited by pirenzepine and the acetylcholine synthesis inhibitor hemicholinium. The results support the cholinergic hypothesis of learning and memory and indicate that M1 receptor agonists and M2 receptor antagonists are likely to prove beneficial in memory deficits. The data also indicates that the clinical dose of some drugs, like physostigmine, needs to be carefully established for optimum therapeutic benefit.

Animals↗

Ontogeny of passive avoidance learning in domestic chicks: punishment of key-peck and running responses.

The effect of the number of prepunishment acquisition trials on the age dependency of passive avoidance (PA) learning of the Vantress X Arbor Acre chick was determined in both key-peck and runway tests. In nine experiments, 1- and 4-day-old chicks were first trained to respond for heat reward, and then, following a variable number of reinforced acquisition trials, the chicks' responses were punished with aversive wing shocks. The major finding of these experiments was that the age dependency of PA learning of the young chick is related specifically to the number of reinforced training trials given prior to PA testing. When a large number of prepunishment acquisition trials were given, 1-day-old chicks learned as quickly as 4-day-old chicks to withhold responding when punished. However, when only a few acquisition trials preceded PA testing, 1-day-old chicks showed significantly less response suppression than 4-day-old chicks. These acquisition effects indicate that the age-dependent changes in PA learning of the chick are not solely due to developmental changes in general inhibitory ability. Rather, these PA results suggest that the 1-day-old chick, compared with the 4-day-old chick, is deficient in learning, or detecting changes in, stimulus- and/or response-reinforcement contingencies.

Aging↗

Tetrahydroaminoacridine facilitates passive avoidance learning in rats with nucleus basalis magnocellularis lesions.

The effect of bilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM) on performance in a step-through passive avoidance task and the ability of tetrahydroaminoacridine (THA) to enhance learning were evaluated. Fischer 344 rats were used in a passive avoidance task in which footshock was replaced by ultrasound (30-62 K Hz, 125 dB) as the aversive training stimulus. THA was given immediately after each single daily training trial and retention was tested 24 hr later for 10 consecutive days. Although NBM lesions alone did not impair passive avoidance learning, THA at 5 mg/kg (i.p.), but not 1 mg/kg, significantly facilitated latency performance in NBM-lesioned rats.

Aminoacridines↗

Effects of additional cues on passive avoidance learning and extinction in rats with hippocampal lesions.

Following the acquisition of a water-rewarded approach response in a straight runway, the effects of introducing shock in the goal box (passive avoidance - PA) or withdrawing reinforcement (extinction) were compared in hippocampal, cortical, and operated control groups of rats. Under standard test conditions, hippocampal groups were impaired in PA learning and showed strong resistance to extinction, relative to the control groups. When additional cues were provided such that external stimuli associated with goal box events could be easily detected early in the runway, performance differences between the hippocampal and control groups were eliminated in the PA test and significantly reduced in extinction. The results emphasize the inefficient processing by hippocampally-damaged animals of stimulus cues following a shift in experimental contingencies.

Animals↗

Active avoidance learning using brain stimulation applied to the inferior colliculus as negative reinforcement in rats: evidence for latent inhibition.

The inferior colliculus has been implicated in aversive or anxiogenic aspects of defensive behavior. Animals learn to turn off electrical stimulation applied to the inferior colliculus. The purpose of the present study was to determine (1) whether this aversion induced by electrical stimulation can be conditioned to a conditioned stimulus (CS, light) and (2) whether pre-exposure to the CS will diminish the extent of such conditioning, i.e. whether latent inhibition can be established with this paradigm. Rats were placed inside an open field, and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold was used as negative reinforcement and shuttle box illumination as the CS. The rats quickly learned to avoid or terminate the inferior-colliculus stimulation. Furthermore, the performance of the animals in this paradigm was significantly disrupted when they were pre-exposed to 50 presentations of the CS before the session. These data suggest that the inferior colliculus has neural substrates for supporting associative learning and latent inhibition.

Animals↗

Effect of 20(S)-ginsenoside-Rg2 and cyproheptadine on two-way active avoidance learning and memory in rats.

The effects of 20(S)-ginsenoside-Rg2 (GRg2, CAS 52286-74-5) and cyproheptadine (CYP, CAS 129-03-3) on acquisition, retention and retrieval were examined in male Wistar rats using a two-way active avoidance method. Learning and memory were estimated by the avoidance rate (%) and/or latency (s). Acute administration of CYP 1.0 mg/kg i.p. 30 min prior to training produced a significant impairment in acquisition of 3 d learning and 48 h memory by decreasing the rate from 87.9 +/- 2.1, 75.8 +/- 4.9 in saline rats to 55.8 +/- 9.6, 53.4 +/- 8.4, respectively (F(1,14) = 10.7, 14.8, p < 0.01). The CYP administration immediately following the end of training and 30 min before testing produced the impairments in retention of 24 h memory and in retrieval of 48 h memory by decreasing the rate from 86.7 +/- 1.7, 93.3 +/- 2.7 to 55.0 +/- 5.5, 60.0 +/- 6.8, respectively (F(1,12) = 27.2, 10.5, p < 0.01). Repeated administration of GRg2 20 mg/kg i.p. significantly improved the CYP-induced recognitional deficits by increasing the CYP-decreased rate from 55.8 +/- 9.6 to 80.8 +/- 4.2 in d 3 learning acquisition (F(1,14) = 5.6, p < 0.05), from 53.4 +/- 8.4 to 60.0 +/- 8.2 in 48 h memory acquisition (F(1,14) = 7.5, p < 0.05) and from 55.0 +/- 5.5 to 88.3 +/- 2.5 in 24 h memory retention (F(1,12) 27.5, p < 0.01) as well as from 60.0 +/- 6.8 to 85.6 +/- 6.9 in 48 h memory retrieval (F(1,12) = 5.2, p < 0.05), respectively. The results also provide the suggestive evidence that central serotonin may play a positive modulatory role in the acquisition, retention and retrieval of two-way active avoidance responding in rats.

Animals↗