Effects of LSD on classical conditioning as a function of CS-UCS interval: relationship to reflex facilitation

Classical conditioning of the rabbit nictitating membrane response was accomplished by presenting a 100-msec tone CS at intervals 0, 100, 200, 400 and 800 msec before the presentation of a 100-msec shock UCS. In addition, tone-alone trials were used to monitor CR acquisition and shock-alone trials to measure facilitation of the nictitating membrane reflex by the tone CS at the various CS-UCS intervals. LSD at a dose of 13 micrograms/kg (30 nmol/kg) increased the excitatory effects of the shock UCS as measured by a greater frequency and amplitude of UCRs elicited across a wide range of UCS intensities and by the ability of a low intensity shock to produce reflex facilitation. Consequently, LSD produced a higher amplitude of UCRs on UCS-alone trials and on paired trials across all CS-UCS intervals during measurement of tone-induced reflex facilitation. LSD also enhanced CR acquisition across all CS-UCS intervals. Because LSD produced larger amplitude reference UCRs on the UCS-alone trials as compared with controls, calculations of reflex facilitation as a percentage change from these reference amplitudes led to an artifactually smaller effect for the LSD group as compared with controls. Nevertheless, both reflex facilitation as measured prior to CR acquisition on the first day of conditioning and CR acquisition across 10 conditioning sessions were a function of CS-UCS intervals and these two measures were highly correlated in the LSD (+0.94) and vehicle control (+0.85) groups. It was concluded that LSD enhances CR acquisition by enhancing the excitatory effects of both the CS and UCS and thus increasing their ability to enter into associative learning.