Vaginocervical stimulation attenuates the sensitization of appetitive sexual behaviors by estradiol benzoate in the ovariectomized rat.

The acute administration of estradiol benzoate (EB) to the ovariectomized (OVX) rat induces low levels of lordosis while sexually appetitive behaviors (e.g., hops, darts, solicitations) are absent, yet the repeated administration of EB results in a behavioral sensitization in which lordosis is potentiated and sexually appetitive behaviors are induced. We have shown that repeated copulation attenuates the sensitization of appetitive sexual behaviors. Here, we assessed which component of male stimulation during copulation is involved in the attenuation. On 8 occasions, sexually experienced OVX Long-Evans rats were treated with 10µgEB and 48h later assigned to one of six groups that differed in their experience on intermediates tests (2-7). One was given repeated access to a male (EB/Male), and another was placed in the copulation chamber alone (EB/Alone) on intermediate tests. Three groups were given one of three somatosensory stimuli by the experimenter: manual flank stimulation (FLS), clitoral stimulation (CLS), or vaginocervical stimulation (VCS). Finally, the control group was left undisturbed in the animal care facility (ACF). Sexual behaviors were measured on Tests 1 and 8. VCS received from the experimenter (VCS) or from the male during copulation (EB/Male) attenuated the magnitude of the sensitization of appetitive sexual behaviors compared with those that were not brought to the testing rooms (ACF), and the effect was most pronounced on sexual solicitations. These results suggest that VCS received during penile intromission inhibits the sensitization of sexually appetitive behaviors by repeated administration of EB. As such, repeated administration of EB may oppose those mechanisms that induce estrous termination, perhaps by sensitizing inhibitory processes within the ventromedial hypothalamus that typically prevent the display of sexual behaviors (i.e., by facilitating disinhibition).

Acute ethanol disrupts conditioned inhibition in the male rat.

RATIONALE: Alcohol can disrupt conditioned sexual inhibition (CSI) established by first-order conditioning in male rats. CSI can also be induced using second-order conditioning, during which male rats are trained to associate a neutral odor with a nonreceptive female. As a result, when given access to two receptive females (one scented and one unscented) during a copulatory preference test, they display CSI toward the scented female. OBJECTIVE: The present study examined the effect of low-to-moderate doses of alcohol on CSI and brain activation following exposure to alcohol and the olfactory cue alone. METHODS: Sexually-naïve Long-Evans rats received alternate conditioning sessions with unscented receptive or scented (almond extract) non-receptive females. Following the conditioning phase, males were injected with saline, alcohol 0.5 g/kg or 1 g/kg, 45 min before a copulatory test with two receptive females, with one bearing the olfactory cue. Fos activation was later assessed, following exposure to alcohol and the olfactory cue alone, in several brain regions involved in the expression and regulation of male sexual behavior. RESULTS: While males in the saline group displayed sexual avoidance towards the scented female, those injected with alcohol before the copulatory test, regardless of the dose, copulated indiscriminately with both females. Subsequent exposure to alcohol and the olfactory cue alone induced different Fos expression between groups in several brain regions. CONCLUSIONS: Low to moderate doses of alcohol disrupt conditioned sexual inhibition in male rats and induce a differential pattern of neural activation, particularly in regions involved in the expression and regulation of sexual behavior.

Effect of caffeine and adenosine receptor ligands on the expression of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS).

The influence of caffeine on epileptic seizures remains a matter of debate. Here we tested on Genetic Absence Epilepsy Rats from Strasbourg (GAERS) the consequences of acute and chronic exposure to caffeine on the expression of spike-and-wave discharges (SWDs). Since caffeine is a mixed nonspecific A(1) and A(2A) adenosine receptor antagonist, we measured also the influence of antagonists and agonists of these receptors on SWD expression. GAERS were equipped with four cortical electrodes over the frontoparietal cortex and the cumulated duration and number of SWDs were recorded for 120 min after the injection of increasing doses of caffeine, specific antagonists and agonists of A(1) and A(2A) adenosine receptors. The effects of chronic caffeine were also studied. In GAERS, caffeine dose-dependently reduced the cumulated number and duration of SWDs which almost disappeared after the injection of the two highest doses of caffeine, 5 and 10 mg/kg. Likewise, the A(1) and A(2A) adenosine receptor antagonists led to a dose-dependent reduction of SWD expression while the agonists dose-dependently increased SWD expression. Conversely, the chronic exposure to caffeine via drinking water for 15 days did not influence SWD expression. With the exception of the two highest doses of caffeine that largely enhanced activity, all compounds including low doses of caffeine had no effect on locomotor activity of GAERS. These data show that the acute exposure to low doses of caffeine, or A(1) and A(2A) adenosine receptor antagonists reduces SWD expression in GAERS, independently from any effect on motor activity. The chronic exposure of GAERS to caffeine does not affect the expression of epilepsy.

Carisbamate has powerful disease-modifying effects in the lithium-pilocarpine model of temporal lobe epilepsy.

Lithium-pilocarpine, a relevant model of temporal lobe epilepsy was used to test the neuroprotective and antiepileptogenic effects of carisbamate. Status epilepticus (SE) was induced in adult rats by lithium and pilocarpine. Carisbamate (30, 60, 90, and 120 mg/kg) was injected at 1 and 9 h after SE onset and continued twice daily for 6 additional days. The reference groups received diazepam instead of carisbamate. Neuroprotection was assessed during the first 24 h of SE with Fluoro-Jade B and after 14 days with thionine staining. SE severity and epileptic outcome were assessed by video, and surface and depth electroencephalographic recordings. At the two highest doses, carisbamate treatment reduced SE severity; produced strong neuroprotection of hippocampus, ventral cortices, thalamus, and amygdala; prevented mossy fiber sprouting in the dentate gyrus of the hippocampus; and delayed or suppressed the occurrence of spontaneous motor seizures. Rats with no spontaneous motor seizures displayed spike-and-wave discharges that share all the characteristics of absence seizures. In conclusion, carisbamate is able to induce strong neuroprotection and affect the nature of epileptogenic events occurring during and after lithium-pilocarpine status epilepticus, reflecting marked insult- and disease-modifying effects.