Experiments are being conducted to assess the direct effects of abused drugs, or drugs proposed as treatments for drug abuse, on on-going behavior, on brain neurochemistry, as discriminative stimuli and on physiological function. Currently, studies are focusing on cannabinoids, nicotine, the constituents of psychoactive bath salts products (cathinones), cocaine and methamphetamine. 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic stimulant with potent effects on blood pressure (BP) and heart rate (HR) that can lead to serious medical complications.
The aim of the current study was to examine pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats. Male Sprague-Dawley rats received surgically-implanted telemetry transmitters for the measurement of BP and HR. Rats were treated with s.c. drug or vehicle and placed into an isolation cubicle on top of a telemetry receiver that detected cardiovascular parameters for 3 h sessions. Racemic MDPV produced dose-dependent (0.33.0 mg/kg) increases in BP and HR. Over the same dose range, the S(+) enantiomer of MDPV produced effects that were similar to the racemate, while the R(-) enantiomer had no effects. Neither of the hydroxylated phase I metabolites of MDPV produced increases in BP or HR. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3 mg/kg, s.c.) antagonized MDPV-induced increases in BP and HR. The -adrenergic antagonist prazosin (0.3 mg/kg, s.c.) antagonized BP responses following MDPV, while the -adrenergic antagonists propranolol (1 mg/kg, s.c.) and atenolol (1 and 3 mg/kg) antagonized HR responses.Cardiovascular effects of racemic MDPV are mediated by the S(+) enantiomer, while metabolites of the drug do not contribute to cardiovascular stimulation. MDPV produces increases in BP and HR secondary to activation of central sympathetic outflow. Treatment with adrenergic antagonists, particularly mixed-action /-receptor blockers, may be useful in counteracting adverse cardiovascular effects of MDPV in emergency situations. Studies have shown the involvement of cannabinoid (CB) receptors in the behavioral and neurobiological effects of psychostimulants. Most of these studies have focused on the role of CB1 receptors in the psychostimulant effects of cocaine, while very few have investigated the respective role of CB2 receptors. Further studies are warranted to elucidate the extent of CB receptor involvement in the expression of cocaine-induced effects.The role of CB1 and CB2 receptors in the rewarding and motor properties of cocaine was assessed in conditioned place preference, conditioned motor activity, and open field activity in rats.The CB1 receptor antagonist rimonabant (3 mg/kg) decreased the acquisition and the expression of conditioned place preference induced by cocaine (20 mg/kg). Rimonabant inhibited cocaine-elicited conditioned motor activity when administered during the expression of cocaine-induced conditioned place preference. Rimonabant decreased ambulatory and vertical activity induced by cocaine. The CB2 receptor agonist JWH-133 (10 mg/kg) decreased the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 inhibited cocaine-elicited conditioned motor activity when administered during the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 decreased ambulatory activity and abolished vertical activity induced by cocaine. The effects of JWH-133 on cocaine conditioned and stimulated responses were abolished when the CB2 receptor antagonist/inverse agonist AM630 (5 mg/kg) was preadministered.Cannabinoid CB1 and CB2 receptors modulate cocaine-induced rewarding behavior and appear to have opposite roles in the regulation of cocaine's reinforcing and psychomotor effects.
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