Anne-Sophie Rössler

The melanocortin agonist, melanotan II, enhances proceptive sexual behaviors in the female rat

Melanocortins have been reported to play a role in the control of both male and female sexual behavior. The present study examined the effects of melanotan-II (MT-II), a cyclic peptide analogue of alpha-melanocyte stimulating hormone on appetitive and consummatory aspects of female sexual behavior, including aspects of sexual proceptivity (solicitations, hops and darts, ear wiggling, pacing) and receptivity (lordosis). One group of ovariectomized Long-Evans rats (n=7) was primed subcutaneously with estradiol benzoate (EB) and progesterone (P) (10 microg and 500 microg respectively) and another group (n=7) with EB (10 microg) and oil (EB alone). Paced mating tests were performed with sexually experienced males in unilevel chambers, which were bisected by a Plexiglas divider containing three holes, through which only the female could pass. MT-II (1 and 3 mg/kg) or saline was injected intravenously 10 min before each 30-min paced mating test. Each female received the 3 treatments. In females primed with EB+P both doses of MT-II increased the number of hops and darts and ear wiggling significantly, but did not alter pacing or lordosis. With EB alone, no effect of MT-II was observed on any of the parameters measured. These results suggest that P can interact with MT-II to increase proceptive behaviors. Because hops and darts are essentially solicitations, made in close proximity to the male, that indicate a desire on the part of females to receive mounts and intromissions, these data suggest that activation of melanocortin receptors may represent a promising mode of action for the treatment of women with hypoactive sexual desire.

Benzodiazepine receptor inverse agonist-induced kindling of rats alters learning and glutamate binding.

Kindling, recognized as a model of epilepsy, can be obtained by applications of repeated nonconvulsive stimulations that finally lead to generalized seizures. Epileptics often show cognitive impairments. The present work analyzed the learning performance of male Wistar rats kindled with a convulsant inverse agonist of the GABA(A)-benzodiazepine receptor complex, methyl beta-carboline-3-carboxylate (beta-CCM). This compound is also known to have an action on learning processes. It was thus interesting to verify if beta-CCM kindling had the same impairing action on learning as other kindling agents, such as pentylenetetrazol (PTZ). A two-way active-avoidance shuttle-box learning task was chosen, because a deficit was found after PTZ kindling in this learning model. On the other hand, hippocampal glutamate binding, has previously been shown to be modified by both seizures and learning. Thus, the level of glutamate binding was also measured in the present study. Results showed that fully kindled rats had poorer learning performance after the third day of test than controls or not fully kindled animals. L-[3H] glutamate binding to hippocampal membrane fractions of the fully kindled animals was significantly higher when compared with controls, whereas L-[3H] glutamate binding of not fully kindled subjects did not differ from that of controls. Neuronal plasticity changes are a possible explanation for the correlation between kindling, learning deficits, and increased glutamate binding.

Changes in Benzodiazepine Binding in a Subkindling Situation

Summary: Purpose: A low dose of the benzodiazepine receptor inverse agonist methyl β‐carboline‐3‐carboxylate (β‐CCM) (1 mg/kg) was used to assess [3H]‐flumazenil binding in a subkindling situation in Swiss mice.