Jonas A. Gylys

Behavioral suppressant effects of clonidine in strains of normotensive and hypertensive rats

The behavioral effects of orally administered clonidine were investigated in Long--Evans (LE), Sprague--Dawley (SD) or Kyoto Wistar (KW) rats assumed to be normotensive and in NIH spontaneously hypertensive (SH) rats. Although clonidine (0.05-1 mg/kg) resulted in the same qualitative effect, i.e., depression of motor activity, the dose of clonidine required to depress motor activity to 50% of control levels (ED50) tended to vary according to strain. An analysis of variance of the dose response curves for the four strains of rats indicated a significant strain effect. When the effects of clonidine on food-reinforced operant responding were investigated it was observed that SD and SH rats differed with regard to rate and temporal pattering of IRT greater than 20 sec responding. Although oral administration of clonidine (0.006-0.1 mg/kg) produced similar percentage decreases from control in SH and SD rats, and analysis of the temporal patterning of responding indicated differences in responsiveness to the behavioral effects of clonidine. These studies demonstrate strain-related differences in responsiveness to the behavioral suppressant effects of clonidine. Marked differences between genetically hypertensive rats and rats assumed to be normotensive were not evident.

5-HT-Dependent myoclonus in guinea pigs: Mediation through 5-HT1A-5-HT2 receptor interaction

Investigations utilizing agonists for 5-HT receptor subtypes have been conducted to determine which 5-HT receptor subtype(s) subserve myoclonus in the guinea pig. Administration of a nonselective 5-HT agonist such as 5-MeODMT (5-HT1A/5-HT2 agonist) induces a dose-dependent behavior characterized by head jerking at low doses (1-2 mg/kg, SC) and full-blown myoclonus (continuous rhythmic whole-body jerking) at higher doses (2.5-5 mg/kg, SC). In contrast, the selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT2 receptor agonist DOI do not induce myoclonus, and elicit only limited head jerking across an otherwise behaviorally active range of doses (1-5 mg/kg, SC). Importantly, the coadministration of both 8-OH-DPAT and DOI results in the emergence of dose-dependent myoclonic behavior. These data suggest that coactivation of 5-HT1A and 5-HT2 receptors may be required for the induction of myoclonus in the guinea pig.

Further studies on BL-3912A: Effects on avoidance behavior of rats with low baselines and on reaction thresholds to electric footshock

Rats selected for their low performance baselines in an active avoidance shuttle box task were given various doses of R-(-)-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane (BL-3912A), S-amphetamine or piracetam. BL-3912A at 1 mg/kg IP had no significant behavioral effects, while 5 and 10 mg/kg significantly increased the number of avoidance responses without affecting responses during the intertrial interval (ITI). Statistically reliable effects on behavior were not observed following 20 mg/kg of BL-3912A. S-Amphetamine at 0.5 and 1 mg/kg IP also facilitated avoidance responding, but could be differentiated from BL-3912A in that the S-amphetamine significantly increased shuttles during the ITI. S-Amphetamine at 0.1 mg/kg was not effective, while 2 mg/kg increased ITI activity. Piracetam (50 or 200 mg/kg) had no significant effects on avoidance or shuttles during ITI. Using an electric shock titration procedure, BL-3912A at 10 and 20 mg/kg IP had no significant effect on reaction thresholds. Animals receiving 100 mg/kg of p-chlorophenylalanine po for 3 days and tested 2 days later showed hyperalgesia to the electric shock. In summary, BL-3912A facilitated shuttle box avoidance responding of rats with low performance baselines. Behavioral facilitation occurred without concomitant increases in noncontingent activity or apparent changes in reactivity to electric footshock.