ABSTRACT
The role of cholinergic neurotransmission in male rat sexual behavior at the brain level has been studied by several researchers. However, little is known about its role at the spinal cord level. In this study, the effects of the intrathecal (IT) administration of the muscarinic receptor antagonist subtypes (MRAs) methoctramine (Meth), tropicamide (Trop) and 4-DAMP on male rat sexual behavior were evaluated during three ejaculatory series. Meth and Trop are preferring antagonists for the M2/M4 receptor subtypes, and 4-DAMP is a preferring antagonist for the M3 receptor subtype. All the MRAs tested noticeably inhibited male rat copulatory behavior, reflected by a reduction in the number of animals engaging in sexual behavior and a gradual decrease in the number of animals able to ejaculate. Significant increases in intromission latency (IL), ejaculation latency (EL) and post-ejaculatory interval (PEI) were observed. The ranking of inhibitory potency in all recorded parameters was Meth>/=4-DAMP>Trop. In theory, the effects of Meth and Trop could be a result of interaction with M2/M4 receptors. However, given that the M2 receptor constitutes the greatest population of muscarinic receptors at all spinal cord sites and given the high affinity for Meth on M2 receptors, the high potency in the inhibitory effects of Meth is indicative of the special role of M2 spinal receptors in the implementation of this behavior. The weaker effects of Trop could be linked to the smaller population of M4 receptors in the spinal cord, but some interaction with M2 receptors is probable. Since some differences in the pattern of inhibitory response between Meth and 4-DAMP were observed in this and a previous study, a possible role for M3 receptors must be considered. The data obtained in this study confirm the facilitating effect of acetylcholine (ACh) at the spinal cord level on male rat sexual behavior through muscarinic mechanisms, with an important influence on ejaculatory processes. These data support the hypothesis of the modulating role of ACh on male rat sexual behavior at the spinal cord level.
Subject(s)
Muscarinic Antagonists/pharmacology , Sexual Behavior, Animal/drug effects , Spinal Cord/drug effects , Animals , Diamines/pharmacology , Injections, Spinal , Male , Piperidines/pharmacology , Rats , Rats, Wistar , Rotarod Performance Test , Sexual Behavior, Animal/physiology , Spinal Cord/physiology , Tropicamide/pharmacologyABSTRACT
The aim of this study was to determine which of the muscarinic receptor subtypes are involved in the modulation of the urethrogenital reflex (UGR) in male, spinal cord-transected rats. The electromyographic (EMG) responses of the bulbospongiosus muscle (BS) to the topical spinal application of muscarine and the combination of muscarine and the selective muscarine receptor antagonists methoctramine (M2), AFDX (M2), 4DAMP (M3) and tropicamide (M4) were determined before and after the elicitation of UGR by way of the mechanical stimulation of the urethra. When 50- and 100-mug doses of muscarine were applied without urethral stimulation, a rhythmic activity of the BS was observed, similar to the one found when UGR was evoked. The M3 and M4 - but not the M2 - antagonists prevented BS response to muscarine when urethral stimulation was not performed. When UGR was elicited following urethral stimulation muscarine produced an increase in burst duration and a decrease in burst frequency. The M2 antagonist reverted the effects of muscarine on the UGR, while the M3 and M4 antagonists produced a significant increase in the frequency and in the bursts number, when compared to the control muscarine response. The differences observed in BS responses to muscarine and muscarine antagonists before and after UGR elicitation were probably linked to the intrinsic effects of the endogenous acethylcholine (Ach) released after urethral stimulation. The present results suggest a cholinergic modulation of UGR in spinal cord-transected rats mediated by the M2, M3 and M4 muscarinic receptor subtypes.
Subject(s)
Genitalia, Male/physiology , Receptors, Muscarinic/physiology , Reflex/physiology , Spinal Cord Injuries/physiopathology , Urethra/physiology , Animals , Dose-Response Relationship, Drug , Genitalia, Male/drug effects , Male , Muscarinic Agonists/pharmacology , Muscarinic Antagonists/pharmacology , Rats , Rats, Wistar , Reflex/drug effects , Sexual Behavior, Animal/drug effects , Sexual Behavior, Animal/physiology , Thoracic Vertebrae , Urethra/drug effectsABSTRACT
The role of GABAA and GABAB receptors in modulation of excitatory synaptic transmission between motoneurons and terminals from dorsolateral funiculus (DLF) was studied in in vitro spinal cord slices of adult turtles. Muscimol--a GABAA receptor agonist--depressed the monosynaptic excitatory postsynaptic potential (EPSP) induced by stimulation of the DLF and shortened its duration. The input resistance and the membrane time constant also were strongly reduced. The input membrane resistance, the amplitude, and the half-width of the EPSP were reduced at the same rate in the presence of muscimol. Bicuculline--a GABAA receptor antagonist--increased the EPSPs amplitude and the input membrane resistance. The EPSP amplitude ratio elicited by a paired-pulse protocol did not change significantly. Our results suggest that muscimol acts mainly by activation of postsynaptic GABAA receptors located on the motoneuron and the synaptic strength on motoneurons may be modulated by tonic activation of postsynaptic GABAA receptors. Baclofen--a GABAB receptor agonist--also depressed DLF-motoneuron synaptic transmission. However, it did not affect the falling phase of the EPSPs or the motoneuron membrane time constant but induced a small decrement in input resistance. In the presence of baclofen, the amplitude ratio produced by a paired-pulse protocol increased significantly. This suggests that baclofen decreased the synaptic strength by inhibition of neurotransmitter release from the DLF terminals via activation of presynaptic GABAB receptors.
Subject(s)
Motor Neurons/physiology , Receptors, GABA/physiology , Spinal Cord/cytology , Synapses/physiology , Animals , Baclofen/pharmacology , Bicuculline/pharmacology , Electric Stimulation , Electrophysiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , In Vitro Techniques , Motor Neurons/classification , Motor Neurons/drug effects , Muscimol/pharmacology , Picrotoxin/pharmacology , Spinal Cord/physiology , Synapses/drug effects , Synaptic Transmission/physiology , Time Factors , Turtles , gamma-Aminobutyric Acid/metabolismABSTRACT
Axons from receptors in the cat vaginal wall run in the sensory pudendal nerve (SPN), and brief (<10 s) vaginal probing (VP) in the decerebrate cat produces a long-lasting (>1 min) contraction of the triceps surae (TS) muscles. The aim of the present project was to find out whether brief SPN stimulation also produces sustained TS response and, eventually, to study the mechanisms involved in it. Decerebrate female cats were used. In some cats, TS electromyography (EMG) and tension response were recorded; stimulation of left SPN with single or repetitive trains of shocks produced a bilateral TS response that outlasted the stimulus >1 min as VP did. In paralyzed cats (pancuronium; Panc), intracellular recordings were made from hind limb motoneurons (MNs). SPN stimulation produced a depolarization