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PubMed1987

Effects of a selective alpha 1-adrenoceptor agonist, methoxamine, on sexual behavior and penile reflexes.

Methoxamine, an adrenergic agonist with selectivity for the alpha 1-adrenoceptor, when administered intraperitoneally 10 minutes prior to mating tests (1 to 5 mg/kg), effected reductions in the ejaculatory threshold, evidenced by a decrease in the number of intromissions preceding ejaculation. In mounting tests after penile anesthetization, a test which specifically assesses sexual motivation, 3 mg/kg methoxamine was without a stimulatory effect. Further, in penile reflex tests (ex copula) 1 mg/kg methoxamine was without effect, whereas 5 mg/kg decreased the number of erections, cups and flips per test, and increased the incidence of seminal emission. These data indicate a facilitation of the ejaculatory mechanism, both in and ex copula, coupled with an inhibition of erectile responses for moderate doses of methoxamine. Treatment of male rats with the alpha 2-adrenoceptor agonist clonidine (0.25 mg/kg, IP, five minutes pretest) drastically reduced the number of animals exhibiting intromissive and ejaculatory behavior in mating tests. This suppressive effect of clonidine was not prevented by prior treatment with methoxamine (3 mg/kg, 10 minutes pretest and five minutes preclonidine). Further, ST-91, a polar analog of clonidine which does not readily enter the central nervous system, was without effect on male sexual behavior. Since (1) the effects of methoxamine administration are not of similar quality or magnitude to those reported earlier after yohimbine, an alpha 2-adrenoceptor antagonist, (2) since concurrent stimulation of alpha 1- (by methoxamine) and alpha 2- (by clonidine) adrenoceptors is followed by a suppression of sexual behavior similar to that seen after clonidine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effects of the chronic ingestion of therapeutic doses of chlorimipramine on the behavioral action of agonists and antagonists of serotonin in male rats.

Locomotor activity and hole-board exploration (frequency and time spent head-dipping) were impaired in male rats by injecting IP the 5-HT agonists, fluoxetine and 5-HTP. This treatment produced also myoclonus and increased the time spent resting during trials. The chronic ingestion of chlorimipramine (CIM) or the injection of the 5-HT receptor blocker, methysergide (15 mg/kg) prevented the action of the 5-HT agonists on locomotion and resting and blocked the appearance of myoclonus. Both CIM and methysergide prevented to a minor degree the fluoxetine-5-HTP-induced decrease of exploration. The chronic ingestion of CIM clearly potentiated the effects of methysergide on hole-board exploration. Results suggest that the chronic treatment with therapeutic doses of CIM reduces the functional activity of some 5-HT systems in the brain of the rat, probably by blockade of post-synaptic 5-HT receptors. This does not preclude, however, that CIM may also alter some NA systems.

5-Hydroxytryptophan↗
PubMed2004

Behavioral effects of serotonin and serotonin agonists in two crayfish species, Procambarus clarkii and Orconectes rusticus.

Exogenous serotonin elicits several behaviors in Procambarus clarkii, including a flexed, elevated posture, reduced locomotion, and changes in aggressive behavior. We conducted experiments to determine if several serotonin agonists mimicked the behavioral effects of serotonin in two crayfish species, P. clarkii and Orconectes rusticus. Drugs tested were 1-(3-Chlorophenyl)-piperazine dihydrochloride (mCPP), Oxymetazoline, 2,5-dimethoxy-4-iodoamphetamine (DOI), CGS-12066A, and (+/-)-8-hydroxy-2-(di-n-dipropylamino) tetralin (8-OH-DPAT). In P. clarkii, mCPP most closely mimicked the effects of serotonin, significantly increasing the performance of the flexed, elevated posture and reducing locomotion; 8-OH-DPAT significantly reduced locomotion as well. Both of these drugs produced significant increases in elevated posture and decreases in locomotion in O. rusticus, and in this species, the drugs at test concentrations were more effective in eliciting these effects than serotonin. The effects of the drugs on behaviors performed during fighting bouts were variable. In both species, only 8-OH-DPAT significantly reduced several agonistic behaviors, and no agonist or 5-HT itself produced significant increases in agonistic behavior.

Animals↗
PubMed1998

Role of cannabinoid receptors in memory storage.

Studies have shown that delta 9-tetrahydrocannabinol, the principal psychoactive ingredient in marijuana, produces memory deficits similar to those produced by neurochemical lesions of the hippocampus. Such lesions impair performance in short-term spatial memory tasks learned prior to the lesion. Animals trained in the behavioral task following the lesion can still perform the task, but learn a different behavioral strategy. Cannabinoid agonists impair behavioral performance in a delay-dependent manner similar to that produced by lesions, but also shift the behavioral response strategy. A possible role for cannabinoid receptors and endogenous cannabinoids may thus be to regulate the storage (i.e., encoding) of information, as well as the means by which that information is retrieved.

Animals↗
PubMed2002

Effects of long-term moderate alcohol consumption on agonistic and affiliative behavior of socially housed female cynomolgus monkeys (Macaca fascicularis).

RATIONALE: The most widely used drug in the US is alcohol. Most people who use alcohol are light-to-moderate drinkers. One or two drinks/day is thought to be not only safe but potentially health-promoting. However, little is known about the chronic effects of moderate alcohol consumption. Alcohol, even in moderate doses, has immediate and robust effects on behavior. OBJECTIVE: To determine the effects of long-term moderate alcohol consumption on the social interactions of adult monkeys. METHODS: Forty-nine adult, ovariectomized monkeys lived in small, stable social groups for 31 months and voluntarily consumed a 2-drink/day equivalent (0.5 g/kg ethanol), 5 days/week for 24 months. Alcohol was presented in a sweet tasting non-nutritive vehicle to half the monkeys, while the other half received vehicle plus maltose-dextrin isocalorically substituted for alcohol. Social behavior was recorded 1 h before, 1 h after, and 5 h after alcohol. RESULTS: Alcohol caused chronic changes in aggressive and affiliative behavior that were not dependent upon the presence of circulating alcohol. Alcohol increased physical aggression. A subset of the animals was at higher risk for alcohol-induced physical aggression. Alcohol decreased positive affiliative behaviors, increased time spent alone, and increased the frequency of extragroup vigilance. Acutely, alcohol increased the rate of behavioral pathology, i.e. stereotypic behaviors, such as hair plucking, which are normally observed only under adverse environmental conditions. CONCLUSIONS: Long-term moderate alcohol consumption caused chronic deleterious changes in the social interactions of primates in small, stable social groups. These data suggest that chronic moderate alcohol consumption can compromise optimal social interactions in primate species, including human beings.

Aggression↗
PubMed1983

Effects of dopamine depletion on rotational behavior to dopamine agonists.

The contralateral rotation to various dopamine agonists was determined in rats with unilateral lesions of the left nigrostriatal pathway both with and without dopamine depletion caused by dopamine synthesis inhibition. The rotation to drugs possessing D-2 dopamine agonist activity alone was greatly diminished by dopamine depletion. In contrast, the rotation induced by drug possessing D-1 dopamine agonist activity (either D-1 alone or D-1 plus D-2) was affected to a much lesser extent by dopamine depletion.

Animals↗
PubMed1985

Intrahypothalamic effects of progestin agonists on estrous behavior and progestin receptor binding.

To investigate whether metabolism of progesterone (P) to other progestins is necessary for the facilitation of estrous behavior in estrogen-primed rats, we evaluated the behavioral effectiveness of intrahypothalamic implants of two P metabolites, 5 alpha-dihydroprogesterone (DHP) and 20 alpha-hydroxyprogesterone (20HP), and of desoxycorticosterone (DOC). We also determined whether the progestin receptor binding capacity of the steroids correlated with their behavioral efficacy. Implants of DHP and 20HP into the ventromedial hypothalamus were considerably less effective than P in activating estrous behavior; in contrast, the mineralocorticoid DOC was nearly as effective as P. Binding studies showed that P had the highest affinity for brain progestin receptors followed by DHP, DOC and 20HP. Thus there was a poor correlation between the behavioral efficacy and the progestin receptor binding properties of the steroids tested. These data suggest (1) that neither 5 alpha-reduction nor 20 alpha-hydroxylation are necessary for P activation of estrous responsiveness and (2) that the structural features required for the behavior promoting effects of P may not be identical to those required for binding to brain progestin receptors.

20-alpha-Dihydroprogesterone↗
PubMed1998

A global model to define the behavior of partial agonists (bell-shaped dose-response inducers) in pharmacological evaluation of activity in the presence of the full agonist.

The dose-response models for full agonists and for a particular type of partial agonist can be described by sigmoidal curves and bell-shaped curves, respectively. The methods currently used to evaluate the interaction of a full agonist and a partial agonist require a large number of experimental units and base their analysis on nonlinear regression analysis, which may not be statistically appropriate. We propose an appropriate design and a global nonlinear model to evaluate such interactions. The new model allows us to estimate the interaction parameters and the parameters that characterize the individual partial agonist curve and the full agonist curve.

Animals↗
PubMed2005

Impact of activated sludge-derived colloidal organic carbon on behavior of estrogenic agonist recombinant yeast bioassay.

The impact of size-fractionated colloidal organic carbon (COC) originating from a biological wastewater treatment facility on the sensitivity of the yeast estrogen screen (YES) bioassay containing the human estrogen receptor (hER) gene was evaluated. Dose-response curves of serially diluted 17beta-estradiol (E2), both in the presence and absence of COC, were generated by the YES bioassay. The concentration of E2 leading to a 50% YES response (effective concentration 50%, or EC50) was used to evaluate quantitatively the estrogenic activity of the different COC-E2 mixtures. The EC50 values for all COC size fractions, including COC-free samples (<1 kD), were statistically greater than the controls using Milli-Q water. Normalized EC50 values significantly increased as a function of COC concentration for the larger size fractions (>0.22 microm), but were not significantly affected by smaller COC material at environmental levels (1-5 mg/L), while both colloidal polysaccharide concentrations and colloidal fluorophores (measured at an excitation/emission wavelength pair of 350 nm/450 nm) appear to have an important role in the sensitivity of the YES bioassay. Estimates of the colloid-associated E2 fraction did not predict accurately increases in EC50 values. Matrix effects of the specific environment being tested with the YES bioassay need to be evaluated closely due to the sensitivity of the hER and reporter plasmid.

Biological Assay↗
PubMed1985

Inhibition of dopaminergic agonist-induced gnawing behavior by neuroleptic drugs in mice.

Several neuroleptic drugs cause the Parkinsonian syndrome (PS) in humans; however, this effect is not detectable in rodents. PS-inducing drugs inhibit gnawing or biting behavior induced by apomorphine, amphetamine, DOPA, and thozalinone. The effects of five narcoleptic drugs (chlorpromazine, haloperidol, perphenazine, thioridazine, and trifluoperazine) on this behavior were tested in ICR male mice (10 per dose level). The drugs were given ip 30 min before each of the following inducing agents: DL-DOPA (500 mg/kg, iv), apomorphine (100 mg/kg, ip), amphetamine (12.5 mg/kg, ip), and thozalinone (100 mg/kg, ip). The criterion for blocking effectiveness was the prevention of the biting or gnawing behavior. Prevention indexes (PI) were calculated from the LD50/ED50. Data are consistent with the PS-inducing potencies of these five drugs. Another selective index (SI) of each drug was established by the ED50/ND50 ratio. There is some correlation between PI values and clinical symptoms, but it is not as well defined as that between SI values and clinical symptoms. Data from the thozalinone test (SI) appear to provide the best prediction for the PS-inducing potencies of the drugs tested. Thus, this technique appears to be suitable for use as an animal model in preclinical toxicity studies.

Animals↗
PubMed1992

NMDA channel behavior depends on agonist affinity.

We have compared the kinetic properties of NMDA receptor channels activated by exogenous agonists with those activated synaptically. Short (4 msec) applications of L-glutamate to outside-out patches from hippocampal neurons evoked currents that decayed with a double exponential time course that was controlled by both the unbinding rate of agonist and receptor desensitization. Lower-affinity agonists evoked NMDA receptor-activated currents that had faster rates of decay and recovered from desensitization more quickly, consistent with the idea that agonists which dissociate faster allow the receptor to reach a desensitized state less often. Both synaptic and patch responses could be well fitted with a simple kinetic model comprised of two independent but identical binding sites, one open state, one closed state, and one desensitized state, all doubly liganded. Provided that the agonist has a slow unbinding rate relative to the rates into the open and desensitized states (e.g., L-glutamate), this model predicts a response with two decay phases and can thus account for the synaptic response. Since the unbinding rate is the critical determinant of the time course, different affinity transmitters would affect such properties as excitatory postsynaptic current (EPSC) duration. Of the known endogenous excitatory amino acids, only L-glutamate has an affinity for the NMDA receptor consistent with the time course of the EPSC recorded between hippocampal neurons in culture.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Effects of a gonadotropin-releasing hormone agonist on sexual behavior in male rhesus monkeys (Macaca mulatta).

Low levels of sexual behavior persist in male rhesus monkeys treated with GnRH-a despite very low levels of T and gonadotropin that occur during such treatment. The behavior of male rhesus monkeys treated with GnRH-a resembles the behavior of surgically castrated male rhesus monkeys more closely than it does the behavior of reproductively quiescent males during the normal nonmating season. The normal, seasonal cessation of sexual behavior in male rhesus monkeys may result from changes in behavioral sensitivity to circulating androgens.

Animals↗
PubMed2001

Time-dependent actions of D2 family agonist quinpirole on spontaneous behavior in the rat: dissociation between sniffing and locomotion.

RATIONALE: Dopamine agonists elevate locomotion, sniffing, grooming, and a number of other behaviors. However, the D2 family (D2/D3/D4) agonist quinpirole, across a wide dose range, produces a period of locomotor inhibition that precedes the drug's locomotor excitatory effects. OBJECTIVES: The present study asked whether the suppressive actions of quinpirole also extend to other aspects of spontaneous behavior, such as sniffing, rearing and grooming, or whether this suppression of locomotion occurs while the frequency of other behaviors is increased or unaffected. METHODS: Locomotion, sniffing, rearing and grooming were observed over a 150-min test session in rats treated with 0, 0.1, 0.5, 1.0, or 10.0 mg/kg quinpirole. RESULTS: At 0.1 mg/kg, quinpirole suppressed locomotion. Higher doses (0.5-10.0 mg/kg) produced locomotor suppression followed by locomotor excitation. During the period of locomotor suppression, quinpirole also reduced the frequency of rearing and grooming. However, animals under high doses (1 and 10 mg/kg) of quinpirole showed elevated sniffing during the period of locomotor, rear and groom suppression. CONCLUSIONS: These results demonstrate that the well-documented locomotor suppression that precedes quinpirole's excitatory locomotor actions occurs in the midst of active sniffing. These results suggest that the suppressive effects of quinpirole on locomotion do not reflect a state of general behavioral suppression.

Animals↗
PubMed2004

Behavioral sensitization to different dopamine agonists in a parkinsonian rodent model of drug-induced dyskinesias.

Repeated treatment with dopamine (DA) receptor agonists strongly potentiates contralateral turning behavior due to selective stimulation of D1 or D2-class receptors in 6-hydroxydopamine (6-OHDA)-lesioned rats. This phenomenon, referred to as sensitization, is believed to be related to the motor response complications (dyskinesias, on-off states) that occur during chronic administration of levodopa in Parkinson's disease patients. In recent years a new method for the evaluation of abnormal involuntary movements (AIMs) secondary to dopaminergic stimulation in 6-OHDA-lesioned rats was described. These AIMs resemble dyskinesias as seen in parkinsonian patients under levodopa therapy. Our objective was to evaluate the effects of repeated treatment with different regimes of DA agonists on turning behavior and on an AIMs scale in 6-OHDA lesioned rats, with the aim of discriminating between drugs with different dyskinesia-inducing potential. In addition, we explored the effects of a previous exposure to a DA agonist (priming) on the behavioral response to the subsequent administration of a DA agonist with the same or different pharmacologic profile. Our results show that in apomorphine-treated rats, rotational behavior and AIMs run a parallel course of enhancement, while in those receiving quinpirole there is a dissociation, suggesting that they could be mediated by different mechanisms. The finding of a significant priming effect on subsequent testing of 6-OHDA lesioned rats should be borne in mind as the use of these pharmacological tests in the screening of well lesioned animals could lead to an erroneous interpretation of further results on dyskinesias and rotational behavior.

Analysis of Variance↗
PubMed1983

gamma-Butyrolactone effects on behavior induced by dopamine agonists.

gamma-Butyrolactone (GBL) potently inhibits stereotyped behavior induced by indirect (amphetamine and methylphenidate) and direct (apomorphine) dopamine agonists. Amphetamine induces a dose-response partial reversal of the GBL effect. The GABA antagonist, bicuculline, only partially reverses the GBL inhibition of apomorphine activity, indicating that GBL may be acting through mechanisms in addition to effects on GABA.

4-Butyrolactone↗