Methylphenidate and alcohol effects on flash-evoked potentials, body temperature, and behavior in Long-Evans rats.

Methylphenidate (MPD) is a psychostimulant used to treat attention deficit hyperactivity disorder (ADHD). Most adult ADHD patients use ethanol in combination with MPD. This research examined the effects of MPD and ethanol on flash-evoked potentials (FEPs; cortical responses frequently used to assess neural activity and sensory processing) recorded from the visual cortex (VC) and superior colliculus (SC; a structure involved in attention and orientation) of chronically implanted male Long-Evans rats, and on body temperature and open field behavior. For one group of rats, either saline or ethanol (2.0 g/kg) was given 5 min prior to either saline or MPD (2.9 mg/kg). FEPs were recorded 10 and 20 min later. In the VC, ethanol decreased amplitudes of several components, but increased P2. MPD increased N3, but decreased P3 and P4. Ethanol increased the latency of several components. In the SC, ethanol decreased all three components, while MPD increased P3. Ethanol increased latency of all components. During FEP testing, ethanol decreased body movement while MPD increased movement. In the open field, line crossings were increased but rearings were decreased by ethanol. Both ethanol and MPD produced hypothermia. A second group of rats was given MPD at 11.6 mg/kg. Ethanol decreased several VC amplitudes, but increased P2. MPD increased N3 amplitude but decreased amplitude for other components. MPD also counteracted the effect of ethanol on the amplitude of P2 and N3. Both ethanol and MPD increased the latency of several components. In the SC, ethanol decreased all component amplitudes, while MPD increased P3 but decreased N4. Ethanol increased all component latencies, while MPD increased latency for two components. During FEP testing, ethanol decreased body movement while MPD increased movement. In the open field, line crossings were increased by ethanol and MPD. Rearings were eliminated by ethanol in the open field but increased by MPD, and MPD counteracted the effect of ethanol on rearings. Both ethanol and MPD produced hypothermia. Some of these results might help explain why users take MPD and ethanol in combination in order to enable consuming larger amounts of alcohol.

Methylphenidate alters flash-evoked potentials, body temperature, and behavior in Long-Evans rats.

This experiment examined the effects of methylphenidate hydrochloride on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats, as well as on body temperature and open field behavior. FEPs were recorded at 10, 20 and 40 min following intraperitoneal injections of saline, and of doses of 0.7, 2.9, and 11.6 mg/kg methylphenidate on separate days. The 0.7 mg/kg dose did not produce significant effects. In the VC, following administration of the 11.6 mg/kg dose of methylphenidate the amplitude of components P83, N146, and P232 decreased, the amplitude of component N64 briefly increased and components P23, N30, N40, and P48 were unchanged in amplitude. In the SC, component P29 was unaffected, while components P38 and N51 were reduced in amplitude by the 11.6 mg/kg dose of methylphenidate. Peak latencies of components N40, P48, P83, and N146 in the VC and component P38 in the SC were increased by the 11.6 mg/kg dose of methylphenidate. When body temperature was recorded 45 min after drug administration, a mild dose-dependent hypothermia was found with the 2.9 and 11.6 mg/kg methylphenidate doses, suggesting that this may have contributed to the increased latencies. In subsequent open field observations, both line crossings and rearings were significantly increased by the 11.6 mg/kg dose. Increased movement into the center of the testing area was also observed, which could be a sign of increased exploration and reduced anxiety following methylphenidate.

Interactions between mecamylamine and alcohol in Long-Evans rats: flash-evoked potentials, body temperature, behavior, and blood alcohol concentration.

Mecamylamine, a noncompetitive antagonist of nicotinic acetylcholine receptors, has many potential clinical applications, including treating alcohol dependency. However, little is known about the combined effects of mecamylamine and alcohol on visual system electrophysiology. We examined the separate and combined effects of mecamylamine (4.0mg/kg, ip) and alcohol (2.0 g/kg, ip) on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted adult male Long-Evans rats. On separate days, either saline or mecamylamine was given 10 min prior to either saline or ethanol. FEPs were recorded 15 and 30 min after the second injection. In the VC, alcohol significantly decreased the amplitudes of components P23, N29, N39, P89, N143, and P237, but increased P46. N63 amplitude was not significantly altered. In contrast, mecamylamine increased the amplitude of P23, P46, and N63, but reduced the amplitude of N29 and P237. The combination of mecamylamine and alcohol resulted in amplitudes very similar to alcohol alone for components P23, N29, N63, P89, N143, and P237. However, mecamylamine pretreatment reduced the effects of alcohol on components N39 and P46. In the SC, FEP component amplitudes were generally decreased by alcohol but not significantly altered by mecamylamine. Mecamylamine pretreatment did not significantly alter the effects of alcohol on SC amplitudes. Latencies of nearly all components in both structures were significantly increased by all drug treatments, with the greatest increase produced by the combination treatment. Hypothermia was also produced by all drug treatments, with the greatest hypothermia (2.25 °C) produced by the combination treatment, most likely accounting for much of the drug-induced increase in latencies. All drug treatments reduced movement during FEP testing, but later in an open field alcohol increased ambulation while mecamylamine reduced movement. Separate groups of experimentally naïve adult male Holtzman albino and Long-Evans hooded rats were given (ip) either alcohol or mecamylamine plus alcohol. Tail vein samples were taken 30 min later. For both rat strains, blood alcohol concentration in the mecamylamine pretreatment group was significantly less at this time interval by about 50-60 mg/dL, suggesting a mechanism whereby mecamylamine can mitigate some of the acute effects of alcohol (e.g., on VC components N39 and P46).

Effects of mecamylamine on flash-evoked potentials, body temperature, and behavior in Long-Evans rats.

This experiment examined the effects of mecamylamine, a nicotinic acetylcholine receptor antagonist, on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats, and on body temperature and open field behavior. FEPs were recorded at 20 and 35 min following intraperitoneal injections of saline, and of 0.3, 3.0, and 10.0 mg/kg mecamylamine on separate days. The 0.3 mg/kg dose did not produce significant effects. The amplitude of VC components N30, P48, and P87 increased, N150 and P231 decreased, and P23, N40, N58, and N68 were unchanged following administration of the 10.0 mg/kg dose. In the SC, component P28 was unaffected, P39 was reduced, and N49 was augmented by the 10.0 mg/kg dose. All component peak latencies were increased by the 3.0 and 10.0 mg/kg doses. Significant hypothermia was also produced by the 3.0 and 10.0 mg/kg doses, suggesting that this was the basis for the increased latencies. The 10.0 mg/kg dose produced a significant decrease in movement during the recording sessions. In subsequent open field observations, both line crossings and rearings were reduced by the 3.0 and 10.0 mg/kg doses. The results suggest that endogenous acetylcholine acting on nicotinic acetylcholine receptors plays at most a modest role in producing FEPs recorded from the VC and SC.

Baclofen does not counteract the acute effects of ethanol on flash-evoked potentials in Long-Evans rats.

This experiment examined the separate and combined effects of baclofen (5.0 mg/kg, i.p.), a GABA B receptor agonist, and ethanol (2.0 g/kg, i.p.) on flash-evoked potentials (FEPs) recorded from both the visual cortex and superior colliculus (SC) of chronically implanted male Long-Evans rats. In the visual cortex, ethanol significantly decreased the amplitude of positive component P87, but increased P37 and P47. Other component amplitudes were not significantly altered. In contrast, baclofen reduced the amplitude of negative component N31 to such an extent that it became positive. Although P47 was also reduced by baclofen, the amplitude of most other components was increased. Only P24 and P87 were unchanged by baclofen. The combination of baclofen and ethanol resulted in amplitudes very similar to ethanol alone for secondary components P47, N62, and P87, but very similar to baclofen alone for primary component N31 and late components N147 and P230. In the SC, component amplitudes were generally decreased by ethanol, baclofen, and the combination treatment. Latencies of most components in both structures were increased by the drug treatments. Each drug treatment produced significant hypothermia. Locomotor behavior was also altered. These results demonstrate: (1) pharmacological differences between the primary and late components versus the secondary components of the cortical FEP, (2) that baclofen does not counteract significant effects of ethanol on cortical or collicular component amplitudes, and (3) that baclofen enhances N147-P230 amplitude, suggesting reduced cortical arousal.

Baclofen alters flash-evoked potentials in Long-Evans rats.

This experiment examined the effects of the GABA-B agonist baclofen on flash-evoked potentials (FEPs) recorded from both the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats. FEPs were recorded at 5, 25, 45, and 65 min following intraperitoneal injections of saline, and of 1.25, 2.5, 5.0, and 10.0 mg/kg baclofen on separate days. In the VC, the amplitude of components P(23), P(37), N(55), N(150), and P(242) increased, while the amplitude of components N(31) and P(48) decreased following baclofen administration. P(88) was unchanged. In the SC, components P(28), N(49), N(55), and N(59) were reduced in amplitude, while P(39) was unaffected by baclofen. These effects on amplitudes were dose- and time-dependent. Many peak latencies in the VC and SC were altered by baclofen, although there was no obvious pattern of change, with some decreasing, a few increasing, and others unchanged. Body temperature was recorded in a separate group of animals, with both the 5.0 and 10.0 mg/kg doses of baclofen producing significant hypothermia. The 10.0 mg/kg dose of baclofen resulted in a significant decrease in movement during the recording sessions, but not in subsequent open field observations. The results show the involvement of GABA-B receptors in the production/modulation of the various components of FEPs.

Nicotine-ethanol interactions in flash-evoked potentials and behavior of Long-Evans rats.

Although nicotine and ethanol are often used together, little is known about their combined effects on visual system electrophysiology. This experiment examined the separate and combined effects of nicotine and ethanol on flash-evoked potentials (FEPs) recorded from both the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats. There were four treatment conditions administered on separate days: either saline or ethanol (2.0 g/kg, i.p.) was given 10 min before either saline or nicotine (1.0 mg/kg, s.c.). FEPs were recorded at 5, 20, and 40 min following the second injection. In the VC, ethanol significantly decreased the amplitude of most components, but increased P46. Peaks P22 and N53 were unchanged. Nicotine enhanced most component amplitudes, but decreased N29 and P234, while P22 and N139 were unchanged. In the SC, ethanol depressed the amplitude of all components studied. In contrast, nicotine significantly depressed only P27 and N48. Latencies of most components in both structures were increased by ethanol, nicotine, and the combination treatment, although a nicotine-induced enhancement of the effects of ethanol on latencies was not typically observed. Each drug treatment also produced significant hypothermia, with the combination treatment resulting in the greatest hypothermia. Ethanol, either alone or in combination with nicotine, significantly reduced body movements during the FEP recording sessions. In subsequent open-field observations, ethanol, but not nicotine, significantly increased the number of squares crossed, while the combination treatment produced the greatest increase in movement. Nicotine significantly increased rearing behavior, but both ethanol and the combination treatment eliminated rearings. Overall, data suggesting that nicotine can counteract some of the effects of ethanol was demonstrated in varying degrees in the amplitude of VC components N39, P46, N53, N65, and P88, the latency of VC component N53, the amplitude of SC component N59, and the latency of SC components N48 and N54. In contrast, a nicotine-induced enhancement of the effects of ethanol was found for only the latency of VC components N39, P88, and P234, body temperature, and open-field ambulation.

Nicotine alters flash-evoked potentials in Long-Evans rats.

This experiment examined the effects of nicotine on flash-evoked potentials (FEPs) recorded from both the visual cortex (VC) and the superior colliculus (SC) of chronically implanted male Long-Evans rats. FEPs were recorded at 5, 20, 40, and 60 min following subcutaneous injections of saline, and of 0.4, 0.7, and 1.0 mg/kg nicotine on separate days. In the VC, the amplitude of components N(39), N(53), N(67), and P(88) increased, while the amplitude of components N(30) and P(235) decreased following nicotine administration. P(22), P(47), and N(153) were unchanged. In the SC, components P(27), N(48), and N(53) were reduced in amplitude, while P(37) and N(57) were unaffected by nicotine. Many peak latencies in the VC and SC were increased by nicotine, often at all three doses. However, effects of nicotine on FEPs were both dose- and time-dependent. When body temperature was recorded 65 min after drug administration, significant hypothermia was found with both the 0.7- and 1.0-mg/kg nicotine doses. The 1.0-mg/kg dose of nicotine resulted in a significant increase in movement during the recording sessions, but not in subsequent open-field observations. The results demonstrate that nicotinic acetylcholine receptors (nAChRs) play a differential role in the production/modulation of the various components of FEPs.