Online dating, reproductive success and the rise autism spectrum disorder prevalence.

The increase in the prevalence of autism spectrum disorder (ASD) has not yet been adequately explained. There is evidence that when people with a specific personality profile, including strong systematic thinking, attention to detail and lesser social communication skills, though not falling on the autistic spectrum (AS), are more likely to have children with autism, especially when both parents have such characteristics. The use of new technologies such as social networks facilitates the communication of these persons because it does not rely on skills in which they are deficient. We hypothesize that the massive use of such technologies for the establishment of romantic relationships increases the reproductive success of this population contributing to the increase in the prevalence of autism spectrum disorder.

Neurotoxicity in zebrafish exposed to carbon nanotubes: Effects on neurotransmitters levels and antioxidant system.

Given the increasing use of carbon nanotubes (CNT) in several industries and technological applications, it is essential to perform in vivo toxicological studies with these nanomaterials to evaluate their potential ecotoxicity. Dopamine (DA) and serotonin (5HT) are key neurotransmitters for brain functions and behavioral responses. Determination of DA and 5HT were performed in brain samples from zebrafish Danio rerio exposed i.p. to single-walled CNT (SWCNT), besides analyzing acetylcholinesterase (AChE) and ectonucleotidases activity, lipid peroxidation and total antioxidant capacity. Results showed that treatment with SWCNT increased between 3 and 6-fold the concentration of DA and 5HT (p < 0.05). Similarly, a significant reduction (p < 0.05) in AChE activity was observed in the brains of SWCNT exposed zebrafish when compared to the control groups. Cholinergic, serotonergic, and dopaminergic systems, through AChE activity and serotonin and dopamine levels, respectively were affected by SWCNT in the zebrafish brain. Alterations in these neurotransmitters can potentially affect several physiological and behavioral that they control.

Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats.

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

Pharmacological blockage and P2X7 deletion hinder aversive memories: reversion in an enriched environment.

Adenosine triphosphate (ATP) plays a role in cell signaling. It was soon proposed that ATP activates ionotropic P2X receptors, exerting an influence on neurons as well as on glial cells. In addition to the fact that the activation of P2X and P2Y receptors can stimulate or inhibit the release of glutamate from rat hippocampal neurons, the release of ATP has been implicated in hippocampal long-term potentiation (LTP). Through different behavioral paradigms, this study aimed to investigate the participation of P2X7R in genetically modified (knockout (KO)) mice with the suppressed expression of this receptor and in the pharmacological blockage of this receptor in rats, as well as to evaluate the effect of environmental enrichment on potential mnemonic deficits. The results suggest that P2X7R participates in aversive memory processes: pharmacological blockage with the selective P2X7R antagonist, A-740003, in different time frames elicited dose-dependent impairments in memory acquisition, consolidation and retrieval in rats that were submitted to the contextual fear-conditioning (FC) task, and the deletion of P2X7R hampered the aversive memory processes of mice that were subjected to the FC paradigm. Experiments using mice that were subjected to environmental enrichment suggest that this form of stimulation reverses mnemonic impairments that are ascribed to the absence of the P2X7R, suggesting that these receptors do not participate on such a reversal. Finally, no alterations were observed in the habituation memory of P2X7KO mice.

Neuroactive effects of cotinine on the hippocampus: behavioral and biochemical parameters.

The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHßE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays. The extinction of fear memory was significantly improved by both nicotine and its metabolite. Cotinine significantly increased LPO, while nicotine significantly decreased it. Antioxidant capacity was increased by all treatments. Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function. Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine. Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain.

Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus.

Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic monoterpene indole alkaloids. These compounds are able to display a large range of effects on the central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae) leaves, on monoamine levels in rat hippocampus and on monoamine oxidase activity. A significance (p<0.01) of 83.5% reduction in 5-HT levels was observed after intra-hippocampal injection (20 µg/µl). After treatment by intraperitoneal route (10 mg/kg), a 63.4% reduction in 5-HT levels and a 67.4% reduction in DOPAC values were observed. The results indicate that strictosidinic acid seems to act on 5-HT system in rat hippocampus, possibly inhibiting precursor enzymes of 5-HT biosynthesis. The decrease verified in DOPAC levels suggests a role of strictosidinic acid in the dopaminergic transmission, probably due to an inhibition of monoamine oxidase activity, confirmed by the enzymatic assay, which demonstrated an inhibitory effect on MAO A in rat brain mitochondria.

Integrated biological responses of zebrafish (Danio rerio) to analyze water quality in regions under anthropogenic influence.

This study analyzed water quality in regions around Patos lagoon (Southern Brazil) that are under anthropogenic pressure. Water samples were collected from five different sites, including one used as a source for human consumption (COR) and others known to be influenced by human activities (IP). Danio rerio (Teleostei, Cyprinidae) organisms were exposed for 24h to these water samples, plus a control group. It was observed that: (1) reactive oxygen species levels were lower in COR and IP than in the control group; (2) glutamate-cysteine ligase (catalytic subunit) expression was higher in COR than in other sites; (3) exposure to all water samples affected long-term memory (LTM) when compared to control group. Thus, some water samples possess the ability to modulate the antioxidant system and to induce a decline in cognitive functions, as measured by LTM. The obtained results indicate that a combination of variables of different organization level (molecular, biochemical and behavioral) can be employed to analyze water quality in impacted regions.

Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain.

Silymarin (SM), the active complex of milk thistle, is a lipophilic fruit extract and is composed of several isomer flavonolignans. Flavonoids are antioxidants found molecules capable of intercepting reactive oxygen species (ROS). The oxidative stress (OS) is caused by imbalance between antioxidant defenses and production of ROS causing oxidative damage to macromolecules. Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. This study evaluated the effect of SM on biochemical parameters that evaluate OS in aged and young rat brain. For measures of OS were used measures of total oxyradical scavenging capacity (ACAP) through the concentration of ROS by fluorescence, lipid peroxidation (LPO), via FOX and TBARS, proteins oxidation by Western blot (WB). Rats were treated with SM at doses of 200 and 400mg/kg/day (SM200 and SM400). The LPO analyzed through FOX was increased in the hippocampus of aged animals treated with SM400, but in the cortex of young and aged, the highest dose of SM decreased LPO analyzed through TBARS. Both doses have seemed most effective in the reduction of oxidized proteins in aged brain. These results suggest that SM may contribute to the prevention of aged-related and pathological degenerative processes in the brain.

Estradiol valerate and tibolone: effects upon brain oxidative stress and blood biochemistry during aging in female rats.

Estrogen compounds have been described as important brain protectors. This study investigated the effects of estradiol valerate (EV--0.3 mg/kg) and two concentrations of tibolone (TB1=0.5 mg/kg and TB2=1 mg/kg) on brain oxidative stress parameters and blood biochemistry in ovariectomized female rats, of three different age groups (young--2 months, adult--8 months, and old--20 months). In the brain cortex, young and old TB2-treated and old no-hormone-replacement (NR) females showed lower lipid hydroperoxide (LPO) levels compared to young Sham and adult TB1 animals (P<0.05). Also in the cortex, both tibolone doses produced higher (P<0.05) total antioxidant capacity (TOSC) levels compared to EV-treated adult females. Ovariectomized adult females (NR, EV, TB1 and TB2) showed lower (P<0.05) TOSC levels in the hippocampus compared to the Sham control. Reactive oxygen species (ROS) were higher (P<0.05) in old females compared to all younger ones. TB2-treated adults showed higher plasma glucose (P<0.05) levels compared to old animals. Regardless of age, TB2 treatment increased female (P<0.05) LDL levels compared to Sham and EV-treated animals. In old females, TB2 significantly increased HDL levels compared to Sham controls, and decreased triglyceride levels were shown in EV, TB1 and TB2 compared to Sham old females. The Atherogenic Index of Plasma was higher (P<0.05) in adult tibolone-treated females compared to both young and old TB2-treated females. These results suggest that the effects of gonad steroid on brain and blood physiology change significantly with aging, and that evaluating hormonal treatment types and doses could be the key factor in the potential use of a specific hormone therapy.

The benefits and drawbacks of nicotine exposure in the cortex and hippocampus of old rats.

Nicotine is the main alkaloid of tobacco and possesses well-established stimulant effects. Previous reports show that nicotine at low doses improves memory functions, while high doses impair memory. This study aims to analyze the effects of nicotine (NIC) on inhibitory avoidance task and on DNA damage, reactive oxygen species (ROS) concentration, total antioxidant capacity, and lipid peroxidation in cortex and hippocampus of old rats. Male Wistar rats of 24-26 months old (620-700g) were exposed i.p. to two doses (0.3 and 1mg/kg) of NIC daily during 9 days. The treatment NIC 0.3 enhanced long-term memory (p<0.05), whereas NIC 1 improved both short and long-term memories (p<0.05). DNA damage was observed only in hippocampus (p<0.05) after NIC 1 exposure. A similar result was obtained for ROS: higher levels were detected at NIC 1 treatment in hippocampus (p<0.05). No alterations in the total antioxidant capacity were verified after NIC exposure (0.3 and 1mg/kg) in both tissues (p>0.05). Finally, evidence of oxidative damage was observed in terms of lipid peroxides levels, being higher at NIC 1 in hippocampus (p<0.05). Overall the results indicate that deleterious effects paralleled the improved short and long-term memories at the highest NIC dose, since augmented DNA damage, ROS concentration and lipid peroxides levels were registered.

Estradiol valerate and tibolone: effects on memory.

This study investigated the effects of estradiol valerate (EV) and tibolone (TB) treatments on some memory parameters of ovariectomized young (2 months), adult (8 months) and old (20 months) female rats. A Sham-operated group was used as control and the animals were treated daily, by oral gavage, with saline (Sham and placebo NR group), EV (0.3 mg/kg) or TB (0.5 or 1 mg/kg, TB1 and TB2, respectively). In step-down inhibitory avoidance task, the latency of old TB2-treated females in the short-term test was significantly inferior (p<0.05), compared to TB2 adults. In the elevated plus maze, adult NR females spent significantly less time (p<0.05) in the open arms as compared with EV and TB2-treated animals. Additionally, adult TB2-treated females spent significantly less time in the closed arms compared to Sham, NR and TB1 groups. Finally, in the water maze retention test, young TB1-treated animals performed worse when compared to Sham, EV and TB2 females. In the old animals, EV treatment hampered subject performance as compared to all other treatments. Taken together, these results indicate that ovarian hormones differently affect female memory in an age-dependent manner.

Effects of microcystins over short- and long-term memory and oxidative stress generation in hippocampus of rats.

Microcystins produced by cyanobacteria are potent inhibitors of some protein phosphatases, but recent evidence also indicates its potential to generate oxidative stress. In the present study, the effects of microcystin raw extracts (Mic; 0.01 and 20microg/L) and purified okadaic acid (OA; 0.01 and 10microg/L) on short- and long-term memory alteration and antioxidant and oxidative damage were investigated in hippocampus of rats. The results showed an amnesic effect with 0.01 and 20microg/L Mic on retrieval and only with 0.01microg/L Mic on spatial learning. Parallel to these effects oxidative damage was observed as evidenced by augmented levels of lipid peroxides and DNA damage and the absence of antioxidant responses in terms of total oxyradical scavenging capacity. Phase II reactions catalyzed by glutathione-S-transferase were not modified after microcystins exposure. Overall this study showed physiological events (retrieval and spatial learning) that can be related to the classical toxic effects of microcystins (i.e., phosphatase inhibition). In addition, evidence of alternative toxicity mechanisms via oxidative stress generation was also obtained. The fact that organic anion transporter polypeptides (OATP) involved in microcystins uptake are expressed not only in liver but also in brain points to the environmental relevance of the observed effects.

Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat.

The vasorelaxing activity of the aqueous extract of fish Balistes capriscus skin (AEBc) on mesenteric arterial bed (MAB) of rats was studied. The bolus injections of AEBc (bolus of 5.1, 10.2, 20.5, and 41.1mg) significantly inhibited, in a concentration-dependent manner, the maximal contractile response induced by methoxamine (30 microM) in MAB. The vasodilatation action of AEBc is not mediated through beta-adrenoceptors or cyclo-oxigenase, since it was not affected by propranolol (20 microM) or diclofenac sodium (3 microM). The vasodilator response induced by subsequent addition of AEBc Balistes capriscus in bolus was significantly reduced in water infusion for endothelium removal. Treatment with an inhibitor of NO synthase (L-NAME, 10 microM) decreased AEBc effect. The guanylate cyclase inhibitor methylene blue (MB, 100 microM) had no significant effect on AEBc-induced vasodilatation. These results suggest that the vasorelaxing effect of AEBc is mediated by endothelium-dependent (NO/EDRF) and endothelium-independent neurally induced vasorelaxation from nonadrenergic and noncholinergic nerves (NO).

Stress hormones enhance retrieval of fear conditioning acquired either one day or many months before.

It has been known for years that systemic administration of the stress hormones, adrenocorticotrophin (ACTH), lysine-vasopressin, adrenaline, or beta-endorphin, enhances retrieval of aversive behaviours acquired one or a few days before. Here we show that the pre-test i.p. injection of the hormones in rats can also enhance retrieval when given months after the original training. The effectiveness of the treatments changed with time. When animals were tested 3 months after training the hormones enhanced retrieval only at doses five times higher than those needed 1 day after training. Between 6 and 9 months from training the hormones either lost their effect (vasopressin, beta-endorphin) or actually inhibited retrieval (ACTH, adrenaline). The effects of the hormones cannot be explained by a decrease in locomotor activity: none of the treatments had such an effect, as measured in an open field. However, when the animals were tested between 12 and 19 months after training, the hormones once again became as effective as they had been 1 day after training. This was so in spite of the fact that control retention levels became very low with age, probably as a result of extinction. The oscillation of the sensitivity of retrieval to the hormones does not appear to depend on changes in anxiety levels with ageing or to effects of the hormones on locomotor activity.

Bupropion and sertraline enhance retrieval of recent and remote long-term memory in rats.

Wistar rats were trained in step-down inhibitory avoidance at the age of 3 months, and tested for retrieval either 1 day later or 3, 6, 9, 12, 15 or 19 months later, when the animals were 6, 9, 12, 15, 18 or 22 months old, respectively. Bupropion (20 or 60 mg/kg) and sertraline (3.3 or 10 mg/kg) given orally 6 or 3 h before retention testing, respectively, enhanced retrieval of this task at all training-test intervals, despite the fact that retrieval at the longest intervals was practically not seen in control animals. The effect cannot be explained by influences of the drugs on locomotor activity; the treatments had no effect on open field behaviour at the age of 3, 8 or 21 months. The findings may be relevant to the use of these drugs as cognitive enhancers in elderly subjects.

Modulation of working memory and of long- but not short-term memory by cholinergic mechanisms in the basolateral amygdala.

Male Wistar rats were exposed to one-trial step-down inhibitory avoidance training using a 0.5 mA footshock. Through bilaterally implanted indwelling cannulae, they received bilateral 0.5 microl infusions of saline, oxotremorine (0.06 or 0.3 microg) or scopolamine (0.25 or 2.0 microg) into the basolateral complex of the amygdaloid nucleus (BLA). Infusions were either 10 min before training (experiment 1) or 4 min after training (experiment 2). In experiment 1, the animals were tested three times: first for working memory (WM) 2 s after training, then for short-term memory (STM) 1.5 h later, and finally for long-term memory (LTM) 24 h later. Oxotremorine enhanced and scopolamine depressed WM and LTM while leaving STM unaffected. In experiment 2, the treatments were given after WM was presumably over. Again, oxotremorine again enhanced and scopolamine depressed LTM, and neither had any effect on STM. The results fit with the suggestion by Beninger and his co-workers that cholinergic synapses in the BLA regulate WM, generalize that finding to a different task, and show that this mechanism uses muscarinic receptors. In addition, they indicate that the well-known effects of intra-amygdala oxotremorine and scopolamine on LTM are independent of those that the drugs have on WM.

Facilitation and inhibition of retrieval in two aversive tasks in rats by intrahippocampal infusion of agonists of specific glutamate metabotropic receptor subtypes.

RATIONALE: The generic antagonist of glutamate metabotropic receptors (mGlus), MCPG, blocks retrieval of inhibitory avoidance when infused into the CA1 area of rat hippocampus. It was considered important to study the effect of agonists of different types of mGlus on retrieval both of this task and of a related one, contextual fear. OBJECTIVES: To measure the effect of three mGlu agonists (3HPG, which is selective to mGlu1; LCCG, which binds to mGlu2 and mGlu3; and LAP-4, which binds to mGlu4 and mGlu6), infused bilaterally into CA1, on the retrieval of one-trial inhibitory avoidance and contextual fear in rats. METHODS: Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus were trained in one-trial step-down inhibitory avoidance or in a contextual fear task and tested for retention 24 h later. The drugs 3HPG, LCCG and LAP-4 were infused into CA1 at different concentration levels 10 min before retention testing. In addition, we studied the effect of these drugs on locomotor and exploratory activity measured in an open field, and on pro- and anti-conflict behaviour in an elevated plus-maze. RESULTS: 3HPG hindered, and LCCG and LAP-4 enhanced, retrieval of the two tasks. In all cases the effects were dose-dependent. The drugs had no effects on open field or plus maze behaviour. CONCLUSIONS: Retrieval of one-trial inhibitory avoidance and of contextual fear is regulated by mGlus in the CA1area of the rat hippocampus. The results suggest that mGlu2s, mGlu3s, mGlu4s and mGlu6s are necessary for retrieval and that mGlu1s play an inhibitory role. The effects are not explainable by nonspecific influences on locomotor or exploratory activity or anxiety levels.

Simultaneous modulation of retrieval by dopaminergic D(1), beta-noradrenergic, serotonergic-1A and cholinergic muscarinic receptors in cortical structures of the rat.

Retrieval of inhibitory avoidance has been recently shown to require intact glutamate receptors, protein kinases A and C and mitogen-activated protein kinase in the CA1 region of the rat hippocampus and in the entorhinal, posterior parietal and anterior cingulate cortex. These enzymatic activities are known to be modulated by dopamine D(1), beta-noradrenergic, 5HT1A and cholinergic muscarinic receptors. Here we study the effect on retrieval of this task of well-known agonists and antagonists of these receptors infused in the same brain cortical regions and into the basolateral amygdala, in rats. The drugs used were SKF38393 (D(1) agonist), noradrenaline, 8-HO-DPAT (5HT1A agonist), oxotremorine (muscarinic agonist), SCH23390 (D(1) antagonist), timolol (beta antagonist), NAN-190 (5HT1A antagonist) and scopolamine (muscarinic antagonist). All were studied at two different dose levels. The localised infusion of SKF38393, noradrenaline, NAN-190 and oxotremorine into any of the cortical structures mentioned 10 min prior to a 24-h retention test session of one-trial step-down inhibitory avoidance enhanced retention test performance. SCH2330, timolol, 8-HO-DPAT and scopolamine hindered retention test performance. In the basolateral amygdala only an enhancing effect of noradrenaline and an inhibitory effect of timolol were seen. Three hours after the infusions, retention test performance returned to normal in all cases. None of the treatments affected locomotion or rearing in an open field or behaviour in the elevated plus maze. Therefore, their effects on retention testing can be attributed to an influence on retrieval. In conclusion, memory retrieval of this apparently simple task requires the participation of CA1, entorhinal, posterior parietal and anterior cingulate cortex, and is strongly modulated by, dopaminergic D(1), beta-noradrenergic, muscarinic cholinergic and 5HT1A receptors in the four areas. The first three types of receptor enhance, and the latter inhibits, retrieval. Only beta-adrenoceptors appears to be involved in the modulation of retrieval of this task by the amygdala. The results bear on the well-known influence of emotion and mood on retrieval, and indicate that this involves many areas of the brain simultaneously. In addition, the results point to similarities and differences between the modulatory mechanisms that affect retrieval and those involved in the consolidation of the same task.

Novelty enhances retrieval: molecular mechanisms involved in rat hippocampus.

Rats exposed to a novel environment just prior to or 1-2 h, but not 4 or 6 h, before retention testing exhibited an enhanced retrieval of a one-trial inhibitory avoidance training. The bilateral intrahippocampal infusion of PD098059, an inhibitor of mitogen-activated protein kinase (MAPK), the specific upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the novel environment, blocked the enhancing effect of novelty on memory retrieval. In addition, prenovelty infusion of DL-2-amino-5-phosphonovalerate (APV), an antagonist of glutamate NMDA receptors, produced similar effects. The exposure to the novel environment is associated with an activation of p42 and p44 MAPKs and an increase in the phosphorylation state of the transcription factor cAMP response element binding protein (CREB). No changes were observed in cAMP-dependent protein kinase (PKA) activity or in alpha-CAMKII activation. Taken together, our results indicate that novelty activates hippocampal MAPKs, which are necessary, along with glutamate NMDA receptors, for the enhancing effect of novelty on retrieval.

Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning.

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-microl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline), of the glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5), of the protein kinase A inhibitor Rp-cAMPs (0.5 microg/side), of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks.