ABSTRACT
OBJECTIVE: The aim of this study is to demonstrate that monitoring, by means of telemetry technology, the increases in intracavernosal pressure (ICP) in freely moving rats using melanotan-II (MT-II) as a proerectile inducer compound is a relevant experimental model to investigate the effects of pharmacological agents on erection. METHODS: Adult rats were implanted in the corpus cavernosum with a pressure sensor which permitted telemetric monitoring of ICP in freely moving animals following MT-II (0.1, 0.3 and 1 mg/kg) or saline i.v. injections. ICP was also measured after MT-II (0.1, 0.3 or 1 mg/kg) or saline i.v. delivery in anesthetized rats. RESULTS: In conscious rats, MT-II (1 mg/kg) significantly increased overall erectile activity compared to saline. In anesthetized rats, MT-II-induced increase in overall erectile activity was not statistically significant but displayed a similar pattern. CONCLUSIONS: The use of telemetry technology allowed to collect quantifiable and reliable data regarding the proerectile activity of MT-II in physiological conditions. The telemetry model appears suitable for investigating the potential inducer proerectile properties of pharmacological agents.
Subject(s)
Consciousness , Monitoring, Physiologic/methods , Penile Erection/drug effects , Penis/physiology , Peptides, Cyclic/pharmacology , Telemetry , alpha-MSH/analogs & derivatives , Animals , Blood Pressure/physiology , Male , Rats , Rats, Sprague-Dawley , alpha-MSH/pharmacologyABSTRACT
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.
Subject(s)
Carbolines/pharmacology , GABA-A Receptor Agonists , Glutamic Acid/metabolism , Kindling, Neurologic/drug effects , Learning/drug effects , Animals , Hippocampus/drug effects , Hippocampus/metabolism , Male , Rats , Rats, WistarABSTRACT
PURPOSE: A low dose of the benzodiazepine receptor inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM) (1 mg/kg) was used to assess [3H]-flumazenil binding in a subkindling situation in Swiss mice. METHODS: The brains were removed, and benzodiazepine receptor binding was studied every second day over 14 days of administration. RESULTS: With each successive trial, Bmax values showed a steady and significant decrease, whereas Kd values showed a steady and significant increase. Behavioral data showed that at this low dose, actual kindling (seizuring) was not reached at the behavioral level. CONCLUSIONS: The findings suggest that decreased gamma-aminobutyric acid (GABA) inhibition may occur even if behavioral effects of kindling are not observed.