Knockdown of α2C-adrenoceptors in the occipital cortex rescued long-term potentiation in hidden prenatally malnourished rats.

Moderate reduction in the protein content of the mother's diet calorically compensated by carbohydrates (the so-called "hidden" prenatal malnutrition) leads to increased neocortical expression of the α(2C)-adrenoceptor subtype, together with decreased cortical release of noradrenaline and impaired long-term potentiation (LTP) and visuospatial memory performance during the rat postnatal life. In order to study whether overexpression of the α(2C)-adrenoceptor subtype is causally related to the decreased indices of neocortical plasticity found in prenatally malnourished rats, we evaluated the effect of intracortical (occipital cortex) administration of an antisense oligodeoxynucleotide (ODN) raised against the α(2C)-adrenoceptor mRNA on the LTP elicited in vivo in the occipital cortex of hidden prenatally malnourished rats. In addition, we compare the effect of the antisense ODN to that produced by systemical administration of the subtype-nonselective α(2)-adrenoceptor antagonist atipamezole. Prenatal protein malnutrition led to impaired occipital cortex LTP together with increased expression of α(2C)-adrenoceptors (about twice Bmax) in the same cortical region. [(3)H]-rauwolscine binding assay showed that a 7-day intracortical antisense ODN treatment in the malnourished rats resulted in 50% knockdown of α(2C)-adrenoceptor expression and, in addition, completely rescued the ability of the occipital cortex to develop and maintain long-term potentiation. Atipamezole (0.3 mg/kg i.p.) also led to full recovery of neocortical LTP in malnourished rats. The present results argue in favor of our original hypothesis that the deleterious effect of prenatal malnutrition on neocortical plasticity in the adult progeny is in part consequence of increased neocortical α(2C)-adrenoceptor expression. This receptor subtype is known to be involved in the presynaptic control of noradrenaline release from central neurons, a neurotransmitter that critically influences LTP and memory formation.

Antinociceptive effect of stimulating the occipital or retrosplenial cortex in rats.

UNLABELLED: A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon. PERSPECTIVE: This study presents evidence that stimulation of the retrosplenial or occipital cortex produces antinociception in rat models of acute pain. These findings enhance our understanding of the role of the cerebral cortex in control of pain.

Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

Enhancement of central noradrenaline release during development alters the packing density of neurons in the rat occipital cortex.

The effect of chronic yohimbine treatment early in life on packing density of neurons was evaluated in the occipital cortex of young rats. Yohimbine administration to pups between days 5 and 16 of postnatal life (2.5 mg/kg/day i.p.) resulted at 45 days of age in significantly higher neuronal density in layers II-V of the occipital cortex, the effect being more marked in the dorsal region than in the dorsolateral and lateral ones. Results suggest a relationship between enhanced central noradrenaline activity and altered development of the neuropil in the occipital cortex.

Effects of monoamine reuptake blockade on ponto-geniculo-occipital wave activity.

Norepinephrine (NE) and serotonin (5HT) likely inhibit the generation of ponto-geniculo-occipital (PGO) waves. Either desipramine (DMI) or sertraline (SER:1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthyl amine) was administered in the cat for 2.5 weeks to probe noradrenergic and serotonergic mechanisms, respectively. Placebo days were compared with the first day of drug and with days that followed 2.5 weeks of drug (chronic). PGO rates during REM sleep and the preceding transition period were significantly decreased by either chronic DMI or SER. Cat PGO waves resemble waves that accompany alerting to intense or novel stimuli in wakefulness. Depressive disorders in humans have features of hyperarousal; PGO wave suppression by antidepressant drugs may relate to clinical antidepressant actions.